Skip to main content

Advertisement

SpringerLink
Log in

Neuropeptide systems and new treatments for nicotine addiction

  • Review
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction.

Objectives

The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking.

Results

The reviewed studies indicate that several drugs that target neuropeptide systems diminish the rewarding effects of nicotine by preventing the activation of dopaminergic systems. Other peptide-based drugs diminish the hyperactivity of brain stress systems and diminish withdrawal-associated symptom severity. Blockade of hypocretin-1 and nociceptin receptors and stimulation of galanin and neurotensin receptors diminishes the rewarding effects of nicotine. Both corticotropin-releasing factor type 1 and kappa-opioid receptor antagonists diminish dysphoria and anxiety-like behavior associated with nicotine withdrawal and inhibit stress-induced reinstatement of nicotine seeking. Furthermore, blockade of vasopressin 1b receptors diminishes dysphoria during nicotine withdrawal, and melanocortin 4 receptor blockade prevents stress-induced reinstatement of nicotine seeking. The role of neuropeptide systems in nicotine-primed and cue-induced reinstatement is largely unexplored, but there is evidence for a role of hypocretin-1 receptors in cue-induced reinstatement of nicotine seeking.

Conclusion

Drugs that target neuropeptide systems might decrease the euphoric effects of smoking and improve relapse rates by diminishing withdrawal symptoms and improving stress resilience.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adan RA, Tiesjema B, Hillebrand JJ, la Fleur SE, Kas MJ, de Krom M (2006) The MC4 receptor and control of appetite. Br J Pharmacol 149:815–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adermark L, Morud J, Lotfi A, Danielsson K, Ulenius L, Soderpalm B, Ericson M (2016) Temporal rewiring of striatal circuits initiated by nicotine. Neuropsychopharmacology 41:3051–3059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ague C (1973) Nicotine and smoking: effects upon subjective changes in mood. Psychopharmacologia 30:323–328

    Article  CAS  PubMed  Google Scholar 

  • Ashare RL, Kimmey BA, Rupprecht LE, Bowers ME, Hayes MR, Schmidt HD (2016) Repeated administration of an acetylcholinesterase inhibitor attenuates nicotine taking in rats and smoking behavior in human smokers. Transl Psychiatry 6:e713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aston-Jones G (2005) Brain structures and receptors involved in alertness. Sleep Med 6(Suppl 1):S3–S7

    Article  PubMed  Google Scholar 

  • Aydin C, Oztan O, Isgor C (2011) Effects of a selective Y2R antagonist, JNJ-31020028, on nicotine abstinence-related social anxiety-like behavior, neuropeptide Y and corticotropin releasing factor mRNA levels in the novelty-seeking phenotype. Behav Brain Res 222:332–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bailey JE, Papadopoulos A, Diaper A, Phillips S, Schmidt M, van der Ark P, Dourish CT, Dawson GR, Nutt DJ (2011) Preliminary evidence of anxiolytic effects of the CRF1 receptor antagonist R317573 in the 7.5% CO2 proof-of-concept experimental model of human anxiety. J Psychopharmacol 25:1199–1206

    Article  CAS  PubMed  Google Scholar 

  • Bale TL, Chen A (2012) Minireview: CRF and Wylie Vale: a story of 41 amino acids and a Texan with grit. Endocrinology 153:2556–2561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balerio GN, Aso E, Berrendero F, Murtra P, Maldonado R (2004) Delta9-tetrahydrocannabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice. Eur J Neurosci 20:2737–2748

    Article  PubMed  Google Scholar 

  • Bardo MT, Green TA, Crooks PA, Dwoskin LP (1999) Nornicotine is self-administered intravenously by rats. Psychopharmacology 146:290–296

    Article  CAS  PubMed  Google Scholar 

  • Belin D, Everitt BJ (2008) Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum. Neuron 57: 432–441

  • Belluzzi JD, Wang R, Leslie FM (2005) Acetaldehyde enhances acquisition of nicotine self-administration in adolescent rats. Neuropsychopharmacology 30:705–712

    Article  CAS  PubMed  Google Scholar 

  • Benowitz NL (1988) Drug therapy. Pharmacologic aspects of cigarette smoking and nicotine addition. NEnglJMed 319:1318–1330

    Article  CAS  Google Scholar 

  • Benowitz NL (2009) Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 49:57–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benwell ME, Balfour DJ (1979) Effects of nicotine administration and its withdrawal on plasma corticosterone and brain 5-hydroxyindoles. Psychopharmacology 63:7–11

    Article  CAS  PubMed  Google Scholar 

  • Benwell ME, Balfour DJ, Anderson JM (1988) Evidence that tobacco smoking increases the density of (−)-[3H]nicotine binding sites in human brain. J Neurochem 50:1243–1247

    Article  CAS  PubMed  Google Scholar 

  • Berrettini W, Yuan X, Tozzi F, Song K, Francks C, Chilcoat H, Waterworth D, Muglia P, Mooser V (2008) Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking. Mol Psychiatry 13:368–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biala G, Budzynska B (2006) Reinstatement of nicotine-conditioned place preference by drug priming: effects of calcium channel antagonists. Eur J Pharmacol 537:85–93

    Article  CAS  PubMed  Google Scholar 

  • Biala G, Staniak N, Budzynska B (2010) Effects of varenicline and mecamylamine on the acquisition, expression, and reinstatement of nicotine-conditioned place preference by drug priming in rats. Naunyn Schmiedebergs Arch Pharmacol 381:361–370

    Article  CAS  PubMed  Google Scholar 

  • Birks J (2006) Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev: Cd005593

  • Boules M, Oliveros A, Liang Y, Williams K, Shaw A, Robinson J, Fredrickson P, Richelson E (2011) A neurotensin analog, NT69L, attenuates intravenous nicotine self-administration in rats. Neuropeptides 45:9–16

    Article  CAS  PubMed  Google Scholar 

  • Brielmaier J, CG MD, Smith RF (2012) Effects of acute stress on acquisition of nicotine conditioned place preference in adolescent rats: a role for corticotropin-releasing factor 1 receptors. Psychopharmacology 219:73–82

    Article  CAS  PubMed  Google Scholar 

  • Brown ZW, Amit Z, Rockman GE (1979) Intraventricular self-administration of acetaldehyde, but not ethanol, in naive laboratory rats. Psychopharmacology 64:271–276

    Article  CAS  PubMed  Google Scholar 

  • Bruchas MR, Land BB, Chavkin C (2010) The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors. Brain Res 1314:44–55

    Article  CAS  PubMed  Google Scholar 

  • Bruijnzeel AW (2009) Kappa-opioid receptor signaling and brain reward function. Brain Res Rev 62:127–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruijnzeel AW (2012) Tobacco addiction and the dysregulation of brain stress systems. NeurosciBiobehavRev 36:1418–1441

    CAS  Google Scholar 

  • Bruijnzeel AW, Gold MS (2005) The role of corticotropin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence. Brain Res Brain Res Rev 49:505–528

    Article  CAS  PubMed  Google Scholar 

  • Bruijnzeel AW, Markou A (2004) Adaptations in cholinergic transmission in the ventral tegmental area associated with the affective signs of nicotine withdrawal in rats. Neuropharmacology 47:572–579

    Article  CAS  PubMed  Google Scholar 

  • Bruijnzeel AW, Stam R, Compaan JC, Croiset G, Akkermans LM, Olivier B, Wiegant VM (1999) Long-term sensitization of Fos-responsivity in the rat central nervous system after a single stressful experience. Brain Res 819:15–22

    Article  CAS  PubMed  Google Scholar 

  • Bruijnzeel AW, Lewis B, Bajpai LK, Morey TE, Dennis DM, Gold M (2006) Severe deficit in brain reward function associated with fentanyl withdrawal in rats. Biol Psychiatry 59:477–480

    Article  CAS  PubMed  Google Scholar 

  • Bruijnzeel AW, Zislis G, Wilson C, Gold MS (2007) Antagonism of CRF receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats. Neuropsychopharmacology 32:955–963

    Article  CAS  PubMed  Google Scholar 

  • Bruijnzeel AW, Prado M, Isaac S (2009) Corticotropin-releasing factor-1 receptor activation mediates nicotine withdrawal-induced deficit in brain reward function and stress-induced relapse. BiolPsychiatry 66:110–117

    CAS  Google Scholar 

  • Bruijnzeel AW, Bishnoi M, van Tuijl IA, Keijzers KF, Yavarovich KR, Pasek TM, Ford J, Alexander JC, Yamada H (2010) Effects of prazosin, clonidine, and propranolol on the elevations in brain reward thresholds and somatic signs associated with nicotine withdrawal in rats. Psychopharmacology 212:485–499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruijnzeel AW, Ford J, Rogers JA, Scheick S, Ji Y, Bishnoi M, Alexander JC (2012) Blockade of CRF1 receptors in the central nucleus of the amygdala attenuates the dysphoria associated with nicotine withdrawal in rats. Pharmacol Biochem Behav 101:62–68

    Article  CAS  PubMed  Google Scholar 

  • Bruijnzeel AW, Alexander JC, Perez PD, Bauzo-Rodriguez R, Hall G, Klausner R, Guerra V, Zeng H, Igari M, Febo M (2015) Acute nicotine administration increases BOLD fMRI signal in brain regions involved in reward signaling and compulsive drug intake in rats. Int J Neuropsychopharmacol 18:pyu011

    Article  CAS  Google Scholar 

  • Buczek Y, Le AD, Stewart J, Shaham Y (1999) Stress reinstates nicotine seeking but not sucrose solution seeking in rats. Psychopharmacology 144:183–188

    Article  CAS  PubMed  Google Scholar 

  • Budzynska B, Biala G (2011) Effects of bupropion on the reinstatement of nicotine-induced conditioned place preference by drug priming in rats. Pharmacol Rep 63:362–371

    Article  CAS  PubMed  Google Scholar 

  • Burger C, Gorbatyuk OS, Velardo MJ, Peden CS, Williams P, Zolotukhin S, Reier PJ, Mandel RJ, Muzyczka N (2004) Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. Mol Ther 10:302–317

    Article  CAS  PubMed  Google Scholar 

  • Chaki S, Ogawa S, Toda Y, Funakoshi T, Okuyama S (2003) Involvement of the melanocortin MC4 receptor in stress-related behavior in rodents. Eur J Pharmacol 474:95–101

    Article  CAS  PubMed  Google Scholar 

  • Chavkin C, James IF, Goldstein A (1982) Dynorphin is a specific endogenous ligand of the kappa opioid receptor. Science 215:413–415

    Article  CAS  PubMed  Google Scholar 

  • Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98:437–451

    Article  CAS  PubMed  Google Scholar 

  • Chen R, Lewis KA, Perrin MH, Vale WW (1993) Expression cloning of a human corticotropin-releasing-factor receptor. Proc Natl Acad Sci USA 90:8967–8971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen A, Zorrilla E, Smith S, Rousso D, Levy C, Vaughan J, Donaldson C, Roberts A, Lee KF, Vale W (2006) Urocortin 2-deficient mice exhibit gender-specific alterations in circadian hypothalamus-pituitary-adrenal axis and depressive-like behavior. J Neurosci 26:5500–5510

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Chen J, Williamson VS, An SS, Hettema JM, Aggen SH, Neale MC, Kendler KS (2009) Variants in nicotinic acetylcholine receptors alpha5 and alpha3 increase risks to nicotine dependence. Am J Med Genet B Neuropsychiatr Genet 150b:926–933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiamulera C, Borgo C, Falchetto S, Valerio E, Tessari M (1996) Nicotine reinstatement of nicotine self-administration after long-term extinction. Psychopharmacology 127:102–107

    Article  CAS  PubMed  Google Scholar 

  • Cippitelli A, Rezvani AH, Robinson JE, Eisenberg L, Levin ED, Bonaventure P, Motley ST, Lovenberg TW, Heilig M, Thorsell A (2011) The novel, selective, brain-penetrant neuropeptide Y Y2 receptor antagonist, JNJ-31020028, tested in animal models of alcohol consumption, relapse, and anxiety. Alcohol 45:567–576

    Article  CAS  PubMed  Google Scholar 

  • Cippitelli A, Schoch J, Debevec G, Brunori G, Zaveri NT, Toll L (2016) A key role for the N/OFQ-NOP receptor system in modulating nicotine taking in a model of nicotine and alcohol co-administration. Sci Rep 6:26594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clark SD, Duangdao DM, Schulz S, Zhang L, Liu X, YL X, Reinscheid RK (2011) Anatomical characterization of the neuropeptide S system in the mouse brain by in situ hybridization and immunohistochemistry. J Comp Neurol 519:1867–1893

    Article  CAS  PubMed  Google Scholar 

  • Clemens KJ, Castino MR, Cornish JL, Goodchild AK, Holmes NM (2014) Behavioral and neural substrates of habit formation in rats intravenously self-administering nicotine. Neuropsychopharmacology 39:2584–2593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cohen A, Koob GF, George O (2012) Robust escalation of nicotine intake with extended access to nicotine self-administration and intermittent periods of abstinence. Neuropsychopharmacology 37:2153–2160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cohen A, Treweek J, Edwards S, Leao RM, Schulteis G, Koob GF, George O (2015) Extended access to nicotine leads to a CRF1 receptor dependent increase in anxiety-like behavior and hyperalgesia in rats. Addict Biol 20:56–68

    Article  CAS  PubMed  Google Scholar 

  • Colmers WF, Klapstein GJ, Fournier A, St-Pierre S, Treherne KA (1991) Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor. Br J Pharmacol 102:41–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corey C, Wang B, Johnson SE, Apelberg B, Husten C (2013) Notes from the field: electronic cigarette use among middle and high school students—United States, 2011–2012. MMWR Morb Mortal Wkly Rep 62:729–730

    Google Scholar 

  • Corrigall WA, Coen KM (1989) Nicotine maintains robust self-administration in rats on a limited-access schedule. Psychopharmacology 99:473–478

    Article  CAS  PubMed  Google Scholar 

  • Corrigall WA, Coen KM (1991) Selective dopamine antagonists reduce nicotine self-administration. Psychopharmacology 104:171–176

    Article  CAS  PubMed  Google Scholar 

  • Corrigall WA, Herling S, Coen KM (1989) Evidence for a behavioral deficit during withdrawal from chronic nicotine treatment. Pharmacol Biochem Behav 33:559–562

    Article  CAS  PubMed  Google Scholar 

  • Corrigall WA, Coen KM, Adamson KL (1994) Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res 653:278–284

    Article  CAS  PubMed  Google Scholar 

  • Cosme CV, Gutman AL, LaLumiere RT (2015) The dorsal agranular insular cortex regulates the cued reinstatement of cocaine-seeking, but not food-seeking, behavior in rats. Neuropsychopharmacology 40:2425–2433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crombag HS, Grimm JW, Shaham Y (2002) Effect of dopamine receptor antagonists on renewal of cocaine seeking by reexposure to drug-associated contextual cues. Neuropsychopharmacology 27:1006–1015

    Article  CAS  PubMed  Google Scholar 

  • Cryan JF, Bruijnzeel AW, Skjei KL, Markou A (2003a) Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat. Psychopharmacology 168:347–358

    Article  CAS  PubMed  Google Scholar 

  • Cryan JF, Hoyer D, Markou A (2003b) Withdrawal from chronic amphetamine induces depressive-like behavioral effects in rodents. Biol Psychiatry 54:49–58

    Article  CAS  PubMed  Google Scholar 

  • de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95:322–327

    Article  PubMed  PubMed Central  Google Scholar 

  • de Quidt ME, Emson PC (1986b) Distribution of neuropeptide Y-like immunoreactivity in the rat central nervous system—II. Immunohistochemical analysis. Neuroscience 18:545–618

    Article  PubMed  Google Scholar 

  • Dahlström A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl 232:1–55

    Google Scholar 

  • Damaj MI, Kao W, Martin BR (2003) Characterization of spontaneous and precipitated nicotine withdrawal in the mouse. J Pharmacol Exp Ther 307:526–534

    Article  CAS  PubMed  Google Scholar 

  • Dani JA, Heinemann S (1996) Molecular and cellular aspects of nicotine abuse. Neuron 16:905–908

    Article  CAS  PubMed  Google Scholar 

  • Date Y, Ueta Y, Yamashita H, Yamaguchi H, Matsukura S, Kangawa K, Sakurai T, Yanagisawa M, Nakazato M (1999) Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc Natl Acad Sci USA 96:748–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dawkins L, Turner J, Hasna S, Soar K (2012) The electronic-cigarette: effects on desire to smoke, withdrawal symptoms and cognition. Addict Behav 37:970–973

    Article  PubMed  Google Scholar 

  • De Quidt M, Emson P (1986a) Distribution of neuropeptide Y-like immunoreactivity in the rat central nervous system—I. Radioimmunoassay and chromatographic characterisation. Neuroscience 18:527–543

    Article  CAS  PubMed  Google Scholar 

  • Debruyne D, Sobrio F, Hinschberger A, Camsonne R, Coquerel A, Barre L (2003) Short-term pharmacokinetics and brain distribution of mecamylamine as a preliminary to carbon-11 labeling for nicotinic receptor investigation. JPharmSci 92:1051–1057

    CAS  Google Scholar 

  • Der-Avakian A, Markou A (2012) The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci 35:68–77

    Article  CAS  PubMed  Google Scholar 

  • Dunn AJ, File SE (1987) Corticotropin-releasing factor has an anxiogenic action in the social interaction test. Horm Behav 21:193–202

    Article  CAS  PubMed  Google Scholar 

  • Dunn AJ, Swiergiel AH, Palamarchouk V (2004) Brain circuits involved in corticotropin-releasing factor-norepinephrine interactions during stress. Ann NY Acad Sci 1018:25–34

    Article  CAS  PubMed  Google Scholar 

  • Eaves M, Thatcher-Britton K, Rivier J, Vale W, Koob GF (1985) Effects of corticotropin releasing factor on locomotor activity in hypophysectomized rats. Peptides 6:923–926

    Article  CAS  PubMed  Google Scholar 

  • Egleton RD, Davis TP (2005) Development of neuropeptide drugs that cross the blood-brain barrier. NeuroRx 2:44–53

    Article  PubMed  PubMed Central  Google Scholar 

  • Epping-Jordan MP, Watkins SS, Koob GF, Markou A (1998) Dramatic decreases in brain reward function during nicotine withdrawal. Nature 393:76–79

    Article  CAS  PubMed  Google Scholar 

  • Fadel J, Burk JA (2010) Orexin/hypocretin modulation of the basal forebrain cholinergic system: role in attention. Brain Res 1314:112–123

    Article  CAS  PubMed  Google Scholar 

  • Fagerstrom K, Etter JF, Unger JB (2015) E-cigarettes: a disruptive technology that revolutionizes our field? Nicotine Tob Res 17:125–126

    Article  PubMed  PubMed Central  Google Scholar 

  • Famele M, Ferranti C, Abenavoli C, Palleschi L, Mancinelli R, Draisci R (2014) The chemical components of electronic cigarette cartridges and refill fluids: review of analytical methods. Nicotine & Tobacco Research 17:271–279

    Article  Google Scholar 

  • Finkenauer R, Pomerleau CS, Snedecor SM, Pomerleau OF (2009) Race differences in factors relating to smoking initiation. Addict Behav 34:1056–1059

    Article  PubMed  PubMed Central  Google Scholar 

  • Fletcher PJ, Rizos Z, Noble K, Soko AD, Silenieks LB, Le AD, Higgins GA (2012) Effects of the 5-HT2C receptor agonist Ro60-0175 and the 5-HT2A receptor antagonist M100907 on nicotine self-administration and reinstatement. Neuropharmacology 62:2288–2298

    Article  CAS  PubMed  Google Scholar 

  • Flores RJ, Pipkin JA, Uribe KP, Perez A, O’Dell LE (2016) Estradiol promotes the rewarding effects of nicotine in female rats. Behav Brain Res 307:258–263

    Article  CAS  PubMed  Google Scholar 

  • Fosgerau K, Hoffmann T (2015) Peptide therapeutics: current status and future directions. Drug Discov Today 20:122–128

    Article  CAS  PubMed  Google Scholar 

  • Foulds J, Russ C, CR Y, Zou KH, Galaznik A, Franzon M, Berg A, Hughes JR (2013) Effect of varenicline on individual nicotine withdrawal symptoms: a combined analysis of eight randomized, placebo-controlled trials. Nicotine Tob Res 15:1849–1857

    Article  CAS  PubMed  Google Scholar 

  • Gantz I, Miwa H, Konda Y, Shimoto Y, Tashiro T, Watson SJ, DelValle J, Yamada T (1993) Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J Biol Chem 268:15174–15179

    CAS  PubMed  Google Scholar 

  • George O, Ghozland S, Azar MR, Cottone P, Zorrilla EP, Parsons LH, O’Dell LE, Richardson HN, Koob GF (2007) CRF CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats. Proc Natl Acad Sci USA 104:17198–17203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gold AB, Wileyto EP, Lori A, Conti D, Cubells JF, Lerman C (2012) Pharmacogenetic association of the galanin receptor (GALR1) SNP rs2717162 with smoking cessation. Neuropsychopharmacology 37:1683–1688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grana R, Benowitz N, Glantz SA (2014) E-cigarettes a scientific review. Circulation 129:1972–1986

    Article  PubMed  PubMed Central  Google Scholar 

  • Grieder TE, Herman MA, Contet C, Tan LA, Vargas-Perez H, Cohen A, Chwalek M, Maal-Bared G, Freiling J, Schlosburg JE, Clarke L, Crawford E, Koebel P, Repunte-Canonigo V, Sanna PP, Tapper AR, Roberto M, Kieffer BL, Sawchenko PE, Koob GF, van der Kooy D, George O (2014) VTA CRF neurons mediate the aversive effects of nicotine withdrawal and promote intake escalation. Nat Neurosci 17:1751–1758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gundlach AL (2002) Galanin/GALP and galanin receptors: role in central control of feeding, body weight/obesity and reproduction? Eur J Pharmacol 440:255–268

    Article  CAS  PubMed  Google Scholar 

  • Hall BJ, Slade S, Wells C, Rose JE, Levin ED (2015) Bupropion-varenicline interactions and nicotine self-administration behavior in rats. Pharmacol Biochem Behav 130:84–89

    Article  CAS  PubMed  Google Scholar 

  • Hancock DB, Reginsson GW, Gaddis NC, Chen X, Saccone NL, Lutz SM, Qaiser B, Sherva R, Steinberg S, Zink F, Stacey SN, Glasheen C, Chen J, Gu F, Frederiksen BN, Loukola A, Gudbjartsson DF, Bruske I, Landi MT, Bickeboller H, Madden P, Farrer L, Kaprio J, Kranzler HR, Gelernter J, Baker TB, Kraft P, Amos CI, Caporaso NE, Hokanson JE, Bierut LJ, Thorgeirsson TE, Johnson EO, Stefansson K (2015) Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence. Transl Psychiatry 5: e651.

  • Harrell PT, Marquinez NS, Correa JB, Meltzer LR, Unrod M, Sutton SK, Simmons VN, Brandon TH (2015) Expectancies for cigarettes, e-cigarettes, and nicotine replacement therapies among e-cigarette users (aka vapers). Nicotine Tob Res 17:193–200

    Article  PubMed  Google Scholar 

  • Heilig M, Soderpalm B, Engel JA, Widerlov E (1989) Centrally administered neuropeptide Y (NPY) produces anxiolytic-like effects in animal anxiety models. Psychopharmacology 98:524–529

    Article  CAS  PubMed  Google Scholar 

  • Hikosaka O (2010) The habenula: from stress evasion to value-based decision-making. Nat Rev Neurosci 11:503–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hildebrand BE, Nomikos GG, Hertel P, Schilstrom B, Svensson TH (1998) Reduced dopamine output in the nucleus accumbens but not in the medial prefrontal cortex in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome. Brain Res 779:214–225

    Article  CAS  PubMed  Google Scholar 

  • Hollander JA, Lu Q, Cameron MD, Kamenecka TM, Kenny PJ (2008) Insular hypocretin transmission regulates nicotine reward. Proc Natl Acad Sci USA 105:19480–19485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hopkins TJ, Rupprecht LE, Hayes MR, Blendy JA, Schmidt HD (2012) Galantamine, an acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, attenuates nicotine taking and seeking in rats. Neuropsychopharmacology 37:2310–2321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howard B, Panchal H, McCarthy A, Ashworth A (2005) Identification of the scaramanga gene implicates Neuregulin3 in mammary gland specification. Genes Dev 19:2078–2090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes JR (2007) Effects of abstinence from tobacco: valid symptoms and time course. Nicotine Tob Res 9:315–327

    Article  PubMed  Google Scholar 

  • Hughes JR, Hatsukami D (1986) Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry 43:289–294

    Article  CAS  PubMed  Google Scholar 

  • Hughes JR, Gust SW, Skoog K, Keenan RM, Fenwick JW (1991) Symptoms of tobacco withdrawal. A replication and extension. Arch Gen Psychiatry 48:52–59

    Article  CAS  PubMed  Google Scholar 

  • Hughes JR, Keely J, Naud S (2004) Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction 99:29–38

    Article  PubMed  Google Scholar 

  • Hurst R, Rollema H, Bertrand D (2013) Nicotinic acetylcholine receptors: from basic science to therapeutics. Pharmacol Ther 137:22–54

    Article  CAS  PubMed  Google Scholar 

  • Igari M, Alexander JC, Ji Y, Qi X, Papke RL, Bruijnzeel AW (2013) Varenicline and cytisine diminish the dysphoric-like state associated with spontaneous nicotine withdrawal in rats. Neuropsychopharmacology 39:455–465

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Iijima M, Chaki S (2007) An arginine vasopressin V1b antagonist, SSR149415 elicits antidepressant-like effects in an olfactory bulbectomy model. Prog Neuropsychopharmacol Biol Psychiatry 31:622–627

    Article  CAS  PubMed  Google Scholar 

  • Iijima M, Yoshimizu T, Shimazaki T, Tokugawa K, Fukumoto K, Kurosu S, Kuwada T, Sekiguchi Y, Chaki S (2014) Antidepressant and anxiolytic profiles of newly synthesized arginine vasopressin V1B receptor antagonists: TASP0233278 and TASP0390325. Br J Pharmacol 171:3511–3525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Isola R, Zhang H, Tejwani GA, Neff NH, Hadjiconstantinou M (2008) Dynorphin and prodynorphin mRNA changes in the striatum during nicotine withdrawal. Synapse 62:448–455

    Article  CAS  PubMed  Google Scholar 

  • Jackson KJ, Carroll FI, Negus SS, Damaj MI (2010) Effect of the selective kappa-opioid receptor antagonist JDTic on nicotine antinociception, reward, and withdrawal in the mouse. Psychopharmacology 210:285–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson KJ, Chen X, Miles MF, Harenza J, Damaj MI (2011) The neuropeptide galanin and variants in the GalR1 gene are associated with nicotine dependence. Neuropsychopharmacology 36:2339–2348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson KJ, McLaughlin JP, Carroll FI, Damaj MI (2013) Effects of the kappa opioid receptor antagonist, norbinaltorphimine, on stress and drug-induced reinstatement of nicotine-conditioned place preference in mice. Psychopharmacology 226:763–768

    Article  CAS  PubMed  Google Scholar 

  • Jackson KJ, Jackson A, Carroll FI, Damaj MI (2015) Effects of orally-bioavailable short-acting kappa opioid receptor-selective antagonist LY2456302 on nicotine withdrawal in mice. Neuropharmacology 97:270–274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jarvis MJ (2004) Why people smoke. BMJ 328:277–279

    Article  PubMed  PubMed Central  Google Scholar 

  • Jerlhag E, Engel JA (2011) Ghrelin receptor antagonism attenuates nicotine-induced locomotor stimulation, accumbal dopamine release and conditioned place preference in mice. Drug Alcohol Depend 117:126–131

    Article  CAS  PubMed  Google Scholar 

  • Johnson JG, Cohen P, Pine DS, Klein DF, Kasen S, Brook JS (2000) Association between cigarette smoking and anxiety disorders during adolescence and early adulthood. JAMA 284:2348–2351

    Article  CAS  PubMed  Google Scholar 

  • Johnson PM, Hollander JA, Kenny PJ (2008) Decreased brain reward function during nicotine withdrawal in C57BL6 mice: evidence from intracranial self-stimulation (ICSS) studies. Pharmacol Biochem Behav 90:409–415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnston LD, O’Malley PM, Miech RA, Bachman JG, Schulenberg JE (2015) Monitoring the future national survey results on drug use: 1975–2014: overview, key findings on adolescent drug use. Institute for Social Research, The University of Michigan, Ann Arbor

    Google Scholar 

  • Kallupi M, Cannella N, Economidou D, Ubaldi M, Ruggeri B, Weiss F, Massi M, Marugan J, Heilig M, Bonnavion P (2010) Neuropeptide S facilitates cue-induced relapse to cocaine seeking through activation of the hypothalamic hypocretin system. Proc Natl Acad Sci 107:19567–19572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaspar AA, Reichert JM (2013) Future directions for peptide therapeutics development. Drug Discov Today 18:807–817

    Article  CAS  PubMed  Google Scholar 

  • Kiba H, Jayaraman A (1994) Nicotine induced c-fos expression in the striatum is mediated mostly by dopamine D1 receptor and is dependent on NMDA stimulation. Brain ResMolBrain Res 23:1–13

    Article  CAS  Google Scholar 

  • Kimmey BA, Rupprecht LE, Hayes MR, Schmidt HD (2014) Donepezil, an acetylcholinesterase inhibitor, attenuates nicotine self-administration and reinstatement of nicotine seeking in rats. Addict Biol 19:539–551

    Article  CAS  PubMed  Google Scholar 

  • King PJ, Widdowson PS, Doods HN, Williams G (1999) Regulation of neuropeptide Y release by neuropeptide Y receptor ligands and calcium channel antagonists in hypothalamic slices. J Neurochem 73:641–646

    Article  CAS  PubMed  Google Scholar 

  • Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660

    Article  CAS  PubMed  Google Scholar 

  • Kokare DM, Dandekar MP, Singru PS, Gupta GL, Subhedar NK (2010) Involvement of alpha-MSH in the social isolation induced anxiety- and depression-like behaviors in rat. Neuropharmacology 58:1009–1018

    Article  CAS  PubMed  Google Scholar 

  • Koob GF (1999) Stress, corticotropin-releasing factor, and drug addiction. Ann NY Acad Sci 897:27–45

    Article  CAS  PubMed  Google Scholar 

  • Koob GF, Heinrichs SC (1999) A role for corticotropin releasing factor and urocortin in behavioral responses to stressors. Brain Res 848:141–152

    Article  CAS  PubMed  Google Scholar 

  • Koob GF, Volkow ND (2016) Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry 3:760–773

    Article  PubMed  Google Scholar 

  • Korotkova TM, Sergeeva OA, Eriksson KS, Haas HL, Brown RE (2003) Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins/hypocretins. J Neurosci 23:7–11

    CAS  PubMed  Google Scholar 

  • Lage R, González CR, Diéguez C, López M (2007) Nicotine treatment regulates neuropeptide S system expression in the rat brain. Neurotoxicology 28:1129–1135

    Article  CAS  PubMed  Google Scholar 

  • Lang R, Gundlach AL, Holmes FE, Hobson SA, Wynick D, Hökfelt T, Kofler B (2015) Physiology, signaling, and pharmacology of galanin peptides and receptors: three decades of emerging diversity. Pharmacol Rev 67:118–175

    Article  PubMed  CAS  Google Scholar 

  • LeSage MG, Burroughs D, Dufek M, Keyler DE, Pentel PR (2004) Reinstatement of nicotine self-administration in rats by presentation of nicotine-paired stimuli, but not nicotine priming. Pharmacol Biochem Behav 79:507–513

    Article  CAS  PubMed  Google Scholar 

  • LeSage MG, Burroughs D, Pentel PR (2006) Effects of nicotine withdrawal on performance under a progressive-ratio schedule of sucrose pellet delivery in rats. Pharmacol Biochem Behav 83:585–591

    Article  CAS  PubMed  Google Scholar 

  • Lewis K, Li C, Perrin MH, Blount A, Kunitake K, Donaldson C, Vaughan J, Reyes TM, Gulyas J, Fischer W, Bilezikjian L, Rivier J, Sawchenko PE, Vale WW (2001) Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. ProcNatlAcadSciUSA 98:7570–7575

    Article  CAS  Google Scholar 

  • Liang Y, Boules M, Shaw AM, Williams K, Fredrickson P, Richelson E (2008) Effect of a novel neurotensin analog, NT69L, on nicotine-induced alterations in monoamine levels in rat brain. Brain Res 1231:6–15

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Weiss F (2002) Reversal of ethanol-seeking behavior by D1 and D2 antagonists in an animal model of relapse: differences in antagonist potency in previously ethanol-dependent versus nondependent rats. J Pharmacol Exp Ther 300:882–889

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Caggiula AR, Yee SK, Nobuta H, Poland RE, Pechnick RN (2006) Reinstatement of nicotine-seeking behavior by drug-associated stimuli after extinction in rats. Psychopharmacology 184:417–425

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Caggiula AR, Yee SK, Nobuta H, Sved AF, Pechnick RN, Poland RE (2007) Mecamylamine attenuates cue-induced reinstatement of nicotine-seeking behavior in rats. Neuropsychopharmacology 32:710–718

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Caggiula AR, Palmatier MI, Donny EC, Sved AF (2008) Cue-induced reinstatement of nicotine-seeking behavior in rats: effect of bupropion, persistence over repeated tests, and its dependence on training dose. Psychopharmacology 196:365–375

    Article  CAS  PubMed  Google Scholar 

  • Liu JZ, Tozzi F, Waterworth DM, Pillai SG, Muglia P, Middleton L, Berrettini W, Knouff CW, Yuan X, Waeber G, Vollenweider P, Preisig M, Wareham NJ, Zhao JH, Loos RJ, Barroso I, Khaw KT, Grundy S, Barter P, Mahley R, Kesaniemi A, McPherson R, Vincent JB, Strauss J, Kennedy JL, Farmer A, McGuffin P, Day R, Matthews K, Bakke P, Gulsvik A, Lucae S, Ising M, Brueckl T, Horstmann S, Wichmann HE, Rawal R, Dahmen N, Lamina C, Polasek O, Zgaga L, Huffman J, Campbell S, Kooner J, Chambers JC, Burnett MS, Devaney JM, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Epstein S, Wilson JF, Wild SH, Campbell H, Vitart V, Reilly MP, Li M, Qu L, Wilensky R, Matthai W, Hakonarson HH, Rader DJ, Franke A, Wittig M, Schafer A, Uda M, Terracciano A, Xiao X, Busonero F, Scheet P, Schlessinger D, St Clair D, Rujescu D, Abecasis GR, Grabe HJ, Teumer A, Volzke H, Petersmann A, John U, Rudan I, Hayward C, Wright AF, Kolcic I, Wright BJ, Thompson JR, Balmforth AJ, Hall AS, Samani NJ, Anderson CA, Ahmad T, Mathew CG, Parkes M, Satsangi J, Caulfield M, Munroe PB, Farrall M, Dominiczak A, Worthington J, Thomson W, Eyre S, Barton A, Mooser V, Francks C, Marchini J (2010) Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet 42:436–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lori A, Tang Y, O’Malley S, Picciotto MR, Wu R, Conneely KN, Cubells JF (2011) The galanin receptor 1 gene associates with tobacco craving in smokers seeking cessation treatment. Neuropsychopharmacology 36:1412–1420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lovenberg TW, Liaw CW, Grigoriadis DE, Clevenger W, Chalmers DT, De Souza EB, Oltersdorf T (1995) Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain. Proc Natl Acad Sci USA 92:836–840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lutfy K, Do T, Maidment NT (2001) Orphanin FQ/nociceptin attenuates motor stimulation and changes in nucleus accumbens extracellular dopamine induced by cocaine in rats. Psychopharmacology 154:1–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malin DH (2001) Nicotine dependence: studies with a laboratory model. Pharmacol Biochem Behav 70:551–559

    Article  CAS  PubMed  Google Scholar 

  • Malin DH, Lake JR, Newlin-Maultsby P, Roberts LK, Lanier JG, Carter VA, Cunningham JS, Wilson OB (1992) Rodent model of nicotine abstinence syndrome. Pharmacol Biochem Behav 43:779–784

    Article  CAS  PubMed  Google Scholar 

  • Manbeck KE, Shelley D, Schmidt CE, Harris AC (2014) Effects of oxytocin on nicotine withdrawal in rats. Pharmacol Biochem Behav 116:84–89

    Article  CAS  PubMed  Google Scholar 

  • Mannucci C, Tedesco M, Bellomo M, Caputi AP, Calapai G (2006) Long-term effects of nicotine on the forced swimming test in mice: an experimental model for the study of depression caused by smoke. Neurochem Int 49:481–486

    Article  CAS  PubMed  Google Scholar 

  • Marcinkiewcz CA, Prado MM, Isaac SK, Marshall A, Rylkova D, Bruijnzeel AW (2009) Corticotropin-releasing factor within the central nucleus of the amygdala and the nucleus accumbens shell mediates the negative affective state of nicotine withdrawal in rats. Neuropsychopharmacology 34:1743–1752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marks MJ, Burch JB, Collins AC (1983) Effects of chronic nicotine infusion on tolerance development and nicotinic receptors. J Pharmacol Exp Ther 226:817–825

    CAS  PubMed  Google Scholar 

  • Melander T, Hökfelt T, Rökaeus A (1986) Distribution of galanin-like immunoreactivity in the rat central nervous system. J Comp Neurol 248:475–517

    Article  CAS  PubMed  Google Scholar 

  • Mondal MS, Date Y, Yamaguchi H, Toshinai K, Tsuruta T, Kangawa K, Nakazato M (2005) Identification of ghrelin and its receptor in neurons of the rat arcuate nucleus. Regul Pept 126:55–59

    Article  CAS  PubMed  Google Scholar 

  • Moore RY, Card JP (1984) Noradrenaline-containing neuron systems. In: Bjorklund A, Hokfelt T (eds) Handbook of chemical neuroanatomy. Elsevier Amsterdam, pp 123–156

  • Morgan JI, Curran T (1995) Immediate-early genes: ten years on. Trends Neurosci 18:66–67

    Article  CAS  PubMed  Google Scholar 

  • Myers WD, Ng KT, Singer G (1982) Intravenous self-administration of acetaldehyde in the rat as a function of schedule, food deprivation and photoperiod. Pharmacol Biochem Behav 17:807–811

    Article  CAS  PubMed  Google Scholar 

  • Nakajima M, Inui A, Asakawa A, Momose K, Ueno N, Teranishi A, Baba S, Kasuga M (1998) Neuropeptide Y produces anxiety via Y2-type receptors. Peptides 19:359–363

    Article  CAS  PubMed  Google Scholar 

  • Neugebauer NM, Henehan RM, Hales CA, Picciotto MR (2011) Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference. Pharmacol Biochem Behav 98:87–93

    Article  CAS  PubMed  Google Scholar 

  • Nijsen MJ, Croiset G, Diamant M, de WD, Wiegant VM (2001) CRH signalling in the bed nucleus of the stria terminalis is involved in stress-induced cardiac vagal activation in conscious rats. Neuropsychopharmacology 24: 1–10.

  • Nishizawa D, Kasai S, Hasegawa J, Sato N, Yamada H, Tanioka F, Nagashima M, Katoh R, Satoh Y, Tagami M, Ujike H, Ozaki N, Inada T, Iwata N, Sora I, Iyo M, Yamada M, Kondo N, Won MJ, Naruse N, Uehara-Aoyama K, Itokawa M, Ohi K, Hashimoto R, Tanisawa K, Arai T, Mori S, Sawabe M, Naka-Mieno M, Yamada Y, Yamada M, Sato N, Muramatsu M, Tanaka M, Irukayama-Tomobe Y, Saito YC, Sakurai T, Hayashida M, Sugimura H, Ikeda K (2015) Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies. Mol Brain 8:50

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • O’Connor EC, Parker D, Rollema H, Mead AN (2010) The alpha4beta2 nicotinic acetylcholine-receptor partial agonist varenicline inhibits both nicotine self-administration following repeated dosing and reinstatement of nicotine seeking in rats. Psychopharmacology 208:365–376

    Article  PubMed  CAS  Google Scholar 

  • Ott A, Slooter AJ, Hofman A, van Harskamp F, Witteman JC, Van Broeckhoven C, van Duijn CM, Breteler MM (1998) Smoking and risk of dementia and Alzheimer’s disease in a population-based cohort study: the Rotterdam Study. Lancet 351:1840–1843

    Article  CAS  PubMed  Google Scholar 

  • Pagliusi SR, Tessari M, DeVevey S, Chiamulera C, Pich EM (1996) The reinforcing properties of nicotine are associated with a specific patterning of c-fos expression in the rat brain. Eur J Neurosci 8:2247–2256

    Article  CAS  PubMed  Google Scholar 

  • Panagis G, Hildebrand BE, Svensson TH, Nomikos GG (2000) Selective c-fos induction and decreased dopamine release in the central nucleus of amygdala in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome. Synapse 35:15–25

    Article  CAS  PubMed  Google Scholar 

  • Pañeda C, Huitron-Resendiz S, Frago LM, Chowen JA, Picetti R, de Lecea L, Roberts AJ (2009) Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice. J Neurosci 29:4155–4161

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pang X, Liu L, Ngolab J, Zhao-Shea R, McIntosh JM, Gardner PD, Tapper AR (2016) Habenula cholinergic neurons regulate anxiety during nicotine withdrawal via nicotinic acetylcholine receptors. Neuropharmacology 107:294–304

    Article  CAS  PubMed  Google Scholar 

  • Pape H-C, Jüngling K, Seidenbecher T, Lesting J, Reinscheid RK (2010) Neuropeptide S: a transmitter system in the brain regulating fear and anxiety. Neuropharmacology 58:29–34

    Article  CAS  PubMed  Google Scholar 

  • Pascual MM, Pastor V, Bernabeu RO (2009) Nicotine-conditioned place preference induced CREB phosphorylation and Fos expression in the adult rat brain. Psychopharmacology 207:57–71

    Article  CAS  PubMed  Google Scholar 

  • Pellegrino RM, Tinghino B, Mangiaracina G, Marani A, Vitali M, Protano C, Osborn JF, Cattaruzza MS (2012) Electronic cigarettes: an evaluation of exposure to chemicals and fine particulate matter (PM). Ann Ig 24:279–288

    CAS  PubMed  Google Scholar 

  • Perello M, Dickson SL (2015) Ghrelin signalling on food reward: a salient link between the gut and the mesolimbic system. J Neuroendocrinol 27:424–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perrin MH, Donaldson CJ, Chen R, Lewis KA, Vale WW (1993) Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor. Endocrinology 133:3058–3061

    Article  CAS  PubMed  Google Scholar 

  • Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18:9996–10015

    CAS  PubMed  Google Scholar 

  • Pierce RC, Vanderschuren LJ (2010) Kicking the habit: the neural basis of ingrained behaviors in cocaine addiction. Neurosci Biobehav Rev 35:212–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pirie K, Peto R, Reeves GK, Green J, Beral V (2013) The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. Lancet 381:133–141

    Article  PubMed  PubMed Central  Google Scholar 

  • Plaza-Zabala A, Martin-Garcia E, de Lecea L, Maldonado R, Berrendero F (2010) Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior. J Neurosci 30:2300–2310

  • Plaza-Zabala A, Flores A, Maldonado R, Berrendero F (2012) Hypocretin/orexin signaling in the hypothalamic paraventricular nucleus is essential for the expression of nicotine withdrawal. Biol Psychiatry 71:214–223

    Article  CAS  PubMed  Google Scholar 

  • Plaza-Zabala A, Flores A, Martin-Garcia E, Saravia R, Maldonado R, Berrendero F (2013) A role for hypocretin/orexin receptor-1 in cue-induced reinstatement of nicotine-seeking behavior. Neuropsychopharmacology 38:1724–1736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Postma DS, Bush A, van den Berge M (2015) Risk factors and early origins of chronic obstructive pulmonary disease. Lancet 385:899–909

    Article  PubMed  Google Scholar 

  • Qi X, Shan Z, Ji Y, Guerra V, Alexander JC, Ormerod BK, Bruijnzeel AW (2014) Sustained AAV-mediated overexpression of CRF in the central amygdala diminishes the depressive-like state associated with nicotine withdrawal. Transl Psychiatry 4:e385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qi X, Guzhva L, Ji Y, Bruijnzeel AW (2015a) Chronic treatment with the vasopressin 1b receptor antagonist SSR149415 prevents the dysphoria associated with nicotine withdrawal in rats. Behav Brain Res 292:259–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qi X, Yamada H, Corrie LW, Ji Y, Bauzo RM, Alexander JC, Bruijnzeel AW (2015b) A critical role for the melanocortin 4 receptor in stress-induced relapse to nicotine seeking in rats. Addict Biol 20:324–335

    Article  CAS  PubMed  Google Scholar 

  • Qi X, Guzhva L, Yang Z, Febo M, Shan Z, Wang KK, Bruijnzeel AW (2016) Overexpression of CRF in the BNST diminishes dysphoria but not anxiety-like behavior in nicotine withdrawing rats. Eur Neuropsychopharmacol.

    Google Scholar 

  • Redrobe JP, Dumont Y, Quirion R (2002) Neuropeptide Y (NPY) and depression: from animal studies to the human condition. Life Sci 71:2921–2937

    Article  CAS  PubMed  Google Scholar 

  • Reichmann F, Holzer P (2016) Neuropeptide Y: a stressful review. Neuropeptides 55:99–109

    Article  CAS  PubMed  Google Scholar 

  • Reinscheid RK, Xu YL (2005) Neuropeptide S as a novel arousal promoting peptide transmitter. FEBS J 272:5689–5693

    Article  CAS  PubMed  Google Scholar 

  • Roni MA, Rahman S (2014) The effects of lobeline on nicotine withdrawal-induced depression-like behavior in mice. Psychopharmacology 231:2989–2998

    Article  CAS  PubMed  Google Scholar 

  • Ryan ML, Falk DE, Fertig JB, Rendenbach-Mueller B, Katz DA, Tracy KA, Strain EC, Dunn KE, Kampman K, Mahoney E (2016) A phase 2, double-blind, placebo-controlled randomized trial assessing the efficacy of ABT-436, a novel V1b receptor antagonist, for alcohol dependence. Neuropsychopharmacology.

    Google Scholar 

  • Rylkova D, Boissoneault J, Isaac S, Prado M, Shah HP, Bruijnzeel AW (2008) Effects of NPY and the specific Y1 receptor agonist [D-His(26)]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats. Neuropeptides 42:215–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sajdyk TJ, Vandergriff MG, Gehlert DR (1999) Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of neuropeptide Y in the social interaction test. Eur J Pharmacol 368: 143–147

  • Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585

    Article  CAS  PubMed  Google Scholar 

  • Salas R, Sturm R, Boulter J, De BM (2009) Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice. J Neurosci 29:3014–3018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmoutz CD, Zhang Y, Runyon SP, Goeders NE (2012) Antagonism of the neuropeptide S receptor with RTI-118 decreases cocaine self-administration and cocaine-seeking behavior in rats. Pharmacol Biochem Behav 103:332–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulteis G, Markou A, Cole M, Koob GF (1995) Decreased brain reward produced by ethanol withdrawal. Proc Natl Acad Sci USA 92:5880–5884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Serova LI, Laukova M, Alaluf LG, Sabban EL (2013) Intranasal infusion of melanocortin receptor four (MC4R) antagonist to rats ameliorates development of depression and anxiety related symptoms induced by single prolonged stress. Behav Brain Res 250:139–147

    Article  CAS  PubMed  Google Scholar 

  • Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20

    Article  CAS  PubMed  Google Scholar 

  • Shiffman S, Johnston JA, Khayrallah M, Elash CA, Gwaltney CJ, Paty JA, Gnys M, Evoniuk G, DeVeaugh-Geiss J (2000) The effect of bupropion on nicotine craving and withdrawal. Psychopharmacology 148:33–40

    Article  CAS  PubMed  Google Scholar 

  • Shiffman S, Ferguson SG, Gwaltney CJ, Balabanis MH, Shadel WG (2006) Reduction of abstinence-induced withdrawal and craving using high-dose nicotine replacement therapy. Psychopharmacology 184:637–644

    Article  CAS  PubMed  Google Scholar 

  • Simmons SJ, Gentile TA, Mo L, Tran FH, Ma S, Muschamp JW (2016) Nicotinic receptor blockade decreases fos immunoreactivity within orexin/hypocretin-expressing neurons of nicotine-exposed rats. Behav Brain Res 314:226–233

    Article  CAS  PubMed  Google Scholar 

  • Skjei KL, Markou A (2003) Effects of repeated withdrawal episodes, nicotine dose, and duration of nicotine exposure on the severity and duration of nicotine withdrawal in rats. Psychopharmacology 168:280–292

    Article  CAS  PubMed  Google Scholar 

  • Small E, Shah HP, Davenport JJ, Geier JE, Yavarovich KR, Yamada H, Sabarinath SN, Derendorf H, Pauly JR, Gold MS, Bruijnzeel AW (2010) Tobacco smoke exposure induces nicotine dependence in rats. Psychopharmacology 208:143–158

    Article  CAS  PubMed  Google Scholar 

  • Smith BR, Amit Z, Splawinsky J (1984) Conditioned place preference induced by intraventricular infusions of acetaldehyde. Alcohol 1:193–195

    Article  CAS  PubMed  Google Scholar 

  • Staley JK, Krishnan-Sarin S, Cosgrove KP, Krantzler E, Frohlich E, Perry E, Dubin JA, Estok K, Brenner E, Baldwin RM (2006) Human tobacco smokers in early abstinence have higher levels of β2* nicotinic acetylcholine receptors than nonsmokers. J Neurosci 26:8707–8714

    Article  CAS  PubMed  Google Scholar 

  • Steckler T, Holsboer F (1999) Corticotropin-releasing hormone receptor subtypes and emotion. Biol Psychiatry 46:1480–1508

    Article  CAS  PubMed  Google Scholar 

  • Stolerman IP, Jarvis MJ (1995) The scientific case that nicotine is addictive. Psychopharmacology 117:2–10

    Article  CAS  PubMed  Google Scholar 

  • Sutton RE, Koob GF, Le Moal M, Rivier J, Vale W (1982) Corticotropin releasing factor produces behavioural activation in rats. Nature 297:331–333

    Article  CAS  PubMed  Google Scholar 

  • Suzuki T, Ise Y, Tsuda M, Maeda J, Misawa M (1996) Mecamylamine-precipitated nicotine-withdrawal aversion in rats. Eur J Pharmacol 314:281–284

    Article  CAS  PubMed  Google Scholar 

  • Swalve N, Smethells JR, Carroll ME (2016) Sex differences in attenuation of nicotine reinstatement after individual and combined treatments of progesterone and varenicline. Behav Brain Res 308:46–52

    Article  CAS  PubMed  Google Scholar 

  • Swanson LW, Sawchenko PE, Rivier J, Vale WW (1983) Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 36:165–186

    Article  CAS  PubMed  Google Scholar 

  • Swerdlow NR, Geyer MA, Vale WW, Koob GF (1986) Corticotropin-releasing factor potentiates acoustic startle in rats: blockade by chlordiazepoxide. Psychopharmacology 88:147–152

    Article  CAS  PubMed  Google Scholar 

  • Talhout R, Opperhuizen A, van Amsterdam JG (2006) Sugars as tobacco ingredient: effects on mainstream smoke composition. Food Chem Toxicol 44:1789–1798

    Article  CAS  PubMed  Google Scholar 

  • Talhout R, Opperhuizen A, van Amsterdam JG (2007) Role of acetaldehyde in tobacco smoke addiction. Eur Neuropsychopharmacol 17:627–636

    Article  CAS  PubMed  Google Scholar 

  • Tanaka M, Telegdy G (2008) Antidepressant-like effects of the CRF family peptides, urocortin 1, urocortin 2 and urocortin 3 in a modified forced swimming test in mice. Brain Res Bull 75:509–512

    Article  CAS  PubMed  Google Scholar 

  • Thorgeirsson TE, Steinberg S, Reginsson GW, Bjornsdottir G, Rafnar T, Jonsdottir I, Helgadottir A, Gretarsdottir S, Helgadottir H, Jonsson S, Matthiasson SE, Gislason T, Tyrfingsson T, Gudbjartsson T, Isaksson HJ, Hardardottir H, Sigvaldason A, Kiemeney LA, Haugen A, Zienolddiny S, Wolf HJ, Franklin WA, Panadero A, Mayordomo JI, Hall IP, Ronmark E, Lundback B, Dirksen A, Ashraf H, Pedersen JH, Masson G, Sulem P, Thorsteinsdottir U, Gudbjartsson DF, Stefansson K (2016) A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences. Mol Psychiatry 21:594–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thorsell A, Tapocik JD, Liu K, Zook M, Bell L, Flanigan M, Patnaik S, Marugan J, Damadzic R, Dehdashti SJ, Schwandt ML, Southall N, Austin CP, Eskay R, Ciccocioppo R, Zheng W, Heilig M (2013) A novel brain penetrant NPS receptor antagonist, NCGC00185684, blocks alcohol-induced ERK-phosphorylation in the central amygdala and decreases operant alcohol self-administration in rats. J Neurosci 33:10132–10142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thun MJ, Carter BD, Feskanich D, Freedman ND, Prentice R, Lopez AD, Hartge P, Gapstur SM (2013) 50-year trends in smoking-related mortality in the United States. N Engl J Med 368:351–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turner JR, Ray R, Lee B, Everett L, Xiang J, Jepson C, Kaestner KH, Lerman C, Blendy JA (2014) Evidence from mouse and man for a role of neuregulin 3 in nicotine dependence. Mol Psychiatry 19:801–810

    Article  CAS  PubMed  Google Scholar 

  • Tzschentke TM (1998) Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog Neurobiol 56:613–672

    Article  CAS  PubMed  Google Scholar 

  • Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213:1394–1397

    Article  CAS  PubMed  Google Scholar 

  • Varani AP, Moutinho LM, Bettler B, Balerio GN (2012) Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABA(B1) knockout mice. Neuropharmacology 63:863–872

    Article  CAS  PubMed  Google Scholar 

  • Vazquez-DeRose J, Stauber G, Khroyan TV, Xie XS, Zaveri NT, Toll L (2013) Retrodialysis of N/OFQ into the nucleus accumbens shell blocks cocaine-induced increases in extracellular dopamine and locomotor activity. Eur J Pharmacol 699:200–206

    Article  CAS  PubMed  Google Scholar 

  • Ventura R, Cabib S, Alcaro A, Orsini C, Puglisi-Allegra S (2003) Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine release. J Neurosci 23:1879–1885

    CAS  PubMed  Google Scholar 

  • Walters CL, Brown S, Changeux JP, Martin B, Damaj MI (2006) The beta2 but not alpha7 subunit of the nicotinic acetylcholine receptor is required for nicotine-conditioned place preference in mice. Psychopharmacology 184:339–344

    Article  CAS  PubMed  Google Scholar 

  • Warner C, Shoaib M (2005) How does bupropion work as a smoking cessation aid? Addict Biol 10:219–231

    Article  CAS  PubMed  Google Scholar 

  • Watkins SS, Epping-Jordan MP, Koob GF, Markou A (1999) Blockade of nicotine self-administration with nicotinic antagonists in rats. Pharmacol Biochem Behav 62:743–751

    Article  CAS  PubMed  Google Scholar 

  • Watkins SS, Stinus L, Koob GF, Markou A (2000) Reward and somatic changes during precipitated nicotine withdrawal in rats: centrally and peripherally mediated effects. J Pharmacol Exp Ther 292:1053–1064

    CAS  PubMed  Google Scholar 

  • Wen L, Jiang K, Yuan W, Cui W, Li MD (2016) Contribution of variants in CHRNA5/A3/B4 gene cluster on chromosome 15 to tobacco smoking: from genetic association to mechanism. Mol Neurobiol 53:472–484

    Article  CAS  PubMed  Google Scholar 

  • Wesnes K, Warburton DM (1983) Smoking, nicotine and human performance. Pharmacol Ther 21:189–208

    Article  CAS  PubMed  Google Scholar 

  • WHO (2011) Systematic review of the link between tobacco and poverty. Geneva, Switzerland, World Health Organization

  • WHO (2015) WHO report on the global tobacco epidemic, 2015: raising taxes on tobacco. Geneva, Switzerland, World Health Organization

  • Willis DN, Liu B, Ha MA, Jordt SE, Morris JB (2011) Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. FASEB J 25:4434–4444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woldbye DP, Klemp K, Madsen TM (1998) Neuropeptide Y attenuates naloxone-precipitated morphine withdrawal via Y5-like receptors. J Pharmacol Exp Ther 284:633–636

    CAS  PubMed  Google Scholar 

  • Woldbye DP, Ulrichsen J, Haugbol S, Bolwig TG (2002) Ethanol withdrawal in rats is attenuated by intracerebroventricular administration of neuropeptide Y. Alcohol Alcohol 37:318–321

    Article  CAS  PubMed  Google Scholar 

  • Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, Brucher FA, Zeng J, Ly NK, Henriksen SJ, de Lecea L, Civelli O (2004) Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron 43:487–497

    Article  CAS  PubMed  Google Scholar 

  • Yatawara C, Einfeld S, Hickie I, Davenport T, Guastella A (2015) The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial. Mol Psychiatry 21:1225–1231

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang X, Petruzziello F, Rainer G (2014) Extending the scope of neuropeptidomics in the mammalian brain. EuPA Open Proteomics 3:273–279

    Article  CAS  Google Scholar 

  • Zhao-Shea R, DeGroot SR, Liu L, Vallaster M, Pang X, Su Q, Gao G, Rando OJ, Martin GE, George O, Gardner PD, Tapper AR (2015) Increased CRF signalling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal. Nat Commun 6:6770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zislis G, Desai TV, Prado M, Shah HP, Bruijnzeel AW (2007) Effects of the CRF receptor antagonist D-Phe CRF(12-41) and the alpha2-adrenergic receptor agonist clonidine on stress-induced reinstatement of nicotine-seeking behavior in rats. Neuropharmacology 58:958–966

    Article  CAS  Google Scholar 

  • Zvolensky MJ, Vujanovic AA, Miller MO, Bernstein A, Yartz AR, Gregor KL, McLeish AC, Marshall EC, Gibson LE (2007) Incremental validity of anxiety sensitivity in terms of motivation to quit, reasons for quitting, and barriers to quitting among community-recruited daily smokers. Nicotine Tob Res 9:965–975

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The author (AB) was supported in part by NIH grants DA039349 and DA042530 when working on this review.

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of Florida, 1149 Newell Dr., Gainesville, FL, 32611, USA

    Adriaan W. Bruijnzeel

  2. Department of Neuroscience, University of Florida, Gainesville, FL, USA

    Adriaan W. Bruijnzeel

  3. Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA

    Adriaan W. Bruijnzeel

Authors
  1. Adriaan W. Bruijnzeel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adriaan W. Bruijnzeel.

Ethics declarations

Conflicts of interest

The author declares that he has no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bruijnzeel, A.W. Neuropeptide systems and new treatments for nicotine addiction. Psychopharmacology 234, 1419–1437 (2017). https://doi.org/10.1007/s00213-016-4513-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-016-4513-5

Keywords

Search

Navigation