Skip to main content

Advertisement

SpringerLink
Log in

Effects of Kappa opioid receptor blockade by LY2444296 HCl, a selective short-acting antagonist, during chronic extended access cocaine self-administration and re-exposure in rat

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Cocaine addiction is a chronic brain disease characterized by compulsive drug intake and dysregulation of brain reward systems. Few preclinical studies have modeled the natural longitudinal course of cocaine addiction. Extended access self-administration protocols are powerful tools for modeling the advanced stages of addiction; however, few studies have duration of drug access longer than 12 h/session, potentially limiting their construct validity. Identification of changes in cocaine intake patterns during the development of addictive-like states may allow better treatments for vulnerable subjects. The kappa opioid receptor (KOPr) system has been implicated in the neurobiological regulation of addictive states as well as mood and stress disorders, with selective KOPr antagonists proposed as possible pharmacotherapeutic agents. Chronic cocaine exposure increases the expression of KOPr and its endogenous agonists, the dynorphins, in several brain areas in rodents.

Objectives

To examine the behavioral pattern of intake during chronic (14 days) 18 h intravenous cocaine self-administration (0.5 mg/kg/infusion) and the effect of a novel short-acting KOPr antagonist LY2444296 HCl (3 mg/kg) administered during sessions 8 to 14 of chronic 18 h/day cocaine self-administration and prior to a single re-exposure session after 2 cocaine-free withdrawal days.

Results

Both daily and hourly cocaine intake patterns changed over 14 days of 18 h self-administration. LY pretreatment affected the pattern of self-administration across the second week of extended access cocaine self-administration and prevented the increase in cocaine intake during re-exposure.

Conclusions

Overall, the KOPr antagonist attenuated escalated cocaine consumption in a rat model of extended access cocaine self-administration.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ahmed SH, Koob GF (1998) Transition from moderate to excessive drug intake: change in hedonic set point. Science 282:298–300

    Article  CAS  PubMed  Google Scholar 

  • Ahmed SH, Koob GF (2005) Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function. Psychopharmacology 180:473–490

    Article  CAS  PubMed  Google Scholar 

  • Allain F, Minogianis EA, Roberts DC, Samaha AN (2015) How fast and how often: the pharmacokinetics of drug use are decisive in addiction. Neurosci Biobehav Rev 56:166–179

    Article  PubMed  Google Scholar 

  • Angarita GA, Pittman B, Gueorguieva R, Kalayasiri R, Lynch WJ, Sughondhabirom A, Morgan PT, Malison RT (2010) Regulation of cocaine self-administration in humans: lack of evidence for loading and maintenance phases. Pharmacol Biochem Behav 95:51–55

    Article  CAS  PubMed  Google Scholar 

  • Archer S, Glick SD, Bidlack JM (1996) Cyclazocine revisited. Neurochem Res 21:1369–1373

    Article  CAS  PubMed  Google Scholar 

  • Barros HMT, Miczek KA (1996) Withdrawal from oral cocaine in rats: ultrasonic vocalizations and tactile startle. Psychopharmacology 125:379–384

    Article  CAS  PubMed  Google Scholar 

  • Beardsley PM, Howard JL, Shelton KL, Carroll FI (2005) Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats. Psychopharmacology 183:118–126

    Article  CAS  PubMed  Google Scholar 

  • Beardsley PM, Pollard GT, Howard JL, Carroll FI (2010) Effectiveness of analogs of the kappa opioid receptor antagonist (3R)-7-hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl ]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic) to reduce U50,488-induced diuresis and stress-induced cocaine reinstatement in rats. Psychopharmacology 210:189–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Becker-Krail D, McClung C (2016) Implications of circadian rhythm and stress in addiction vulnerability. F1000Res 5: 59

  • Belej T, Manji D, Sioutis S, Barros HM, Nobrega JN (1996) Changes in serotonin and norepinephrine uptake sites after chronic cocaine: pre- vs. post-withdrawal effects. Brain Res 736:287–296

    Article  CAS  PubMed  Google Scholar 

  • Bouyer JJ, Vallee M, Deminiere JM, Le Moal M, Mayo W (1998) Reaction of sleep-wakefulness cycle to stress is related to differences in hypothalamo-pituitary-adrenal axis reactivity in rat. Brain Res 804:114–124

    Article  CAS  PubMed  Google Scholar 

  • Bozarth MA, Wise RA (1985) Toxicity associated with long-term intravenous heroin and cocaine self-administration in the rat. JAMA 254:81–83

    Article  CAS  PubMed  Google Scholar 

  • Bruchas MR, Yang T, Schreiber S, Defino M, Kwan SC, Li S, Chavkin C (2007) Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase. J Biol Chem 282:29803–29811

    Article  CAS  PubMed  Google Scholar 

  • Butelman ER, Yuferov V, Kreek MJ (2012) Kappa-opioid receptor/dynorphin system: genetic and pharmacotherapeutic implications for addiction. Trends Neurosci 35:587–596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carroll I, Thomas JB, Dykstra LA, Granger AL, Allen RM, Howard JL, Pollard GT, Aceto MD, Harris LS (2004) Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist. Eur J Pharmacol 501:111–119

    Article  CAS  PubMed  Google Scholar 

  • Chartoff EH, Ebner SR, Sparrow A, Potter D, Baker PM, Ragozzino ME, Roitman MF (2016) Relative timing between kappa opioid receptor activation and cocaine determines the impact on reward and dopamine release. Neuropsychopharmacology 41:989–1002

    Article  CAS  PubMed  Google Scholar 

  • Crawford CA, McDougall SA, Bolanos CA, Hall S, Berger SP (1995) The effects of the kappa agonist U-50,488 on cocaine-induced conditioned and unconditioned behaviors and Fos immunoreactivity. Psychopharmacology 120:392–399

    Article  CAS  PubMed  Google Scholar 

  • Domi E, Barbier E, Augier E, Augier G, Gehlert D, Barchiesi R, Thorsell A, Holm L, Heilig M (2018) Preclinical evaluation of the kappa-opioid receptor antagonist CERC-501 as a candidate therapeutic for alcohol use disorders. Neuropsychopharmacology 43:1805–1812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donahue RJ, Landino SM, Golden SA, Carroll FI, Russo SJ, Carlezon WA Jr (2015) Effects of acute and chronic social defeat stress are differentially mediated by the dynorphin/kappa-opioid receptor system. Behav Pharmacol 26:654–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edge PJ, Gold MS (2011) Drug withdrawal and hyperphagia: lessons from tobacco and other drugs. Curr Pharm Des 17:1173–1179

    Article  CAS  PubMed  Google Scholar 

  • Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489

    Article  CAS  PubMed  Google Scholar 

  • Fagergren P, Smith HR, Daunais JB, Nader MA, Porrino LJ, Hurd YL (2003) Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self-administration. Eur J Neurosci 17:2212–2218

    Article  CAS  PubMed  Google Scholar 

  • Falcon E, Ozburn A, Mukherjee S, Roybal K, McClung CA (2013) Differential regulation of the period genes in striatal regions following cocaine exposure. PLoS One 8:e66438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fung YK, Richard LA (1994) Behavioural consequences of cocaine withdrawal in rats. J Pharm Pharmacol 46:150–152

    Article  CAS  PubMed  Google Scholar 

  • Gawin F, Kleber H (1986) Pharmacologic treatments of cocaine abuse. Psychiatr Clin North Am 9:573–583

    Article  CAS  PubMed  Google Scholar 

  • Gehrke BJ, Chefer VI, Shippenberg TS (2008) Effects of acute and repeated administration of salvinorin A on dopamine function in the rat dorsal striatum. Psychopharmacology 197:509–517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glick SD, Maisonneuve IM, Raucci J, Archer S (1995) Kappa opioid inhibition of morphine and cocaine self-administration in rats. Brain Res 681:147–152

    Article  CAS  PubMed  Google Scholar 

  • Glick SD, Visker KE, Maisonneuve IM (1998) Effects of cyclazocine on cocaine self-administration in rats. Eur J Pharmacol 357:9–14

    Article  CAS  PubMed  Google Scholar 

  • Heidbreder CA, Babovic-Vuksanovic D, Shoaib M, Shippenberg TS (1995) Development of behavioral sensitization to cocaine: influence of kappa opioid receptor agonists. J Pharmacol Exp Ther 275:150–163

    CAS  PubMed  Google Scholar 

  • Heidbreder CA, Goldberg SR, Shippenberg TS (1993) The kappa-opioid receptor agonist U-69593 attenuates cocaine-induced behavioral sensitization in the rat. Brain Res 616:335–338

    Article  CAS  PubMed  Google Scholar 

  • Heidbreder CA, Schenk S, Partridge B, Shippenberg TS (1998) Increased responsiveness of mesolimbic and mesostriatal dopamine neurons to cocaine following repeated administration of a selective kappa-opioid receptor agonist. Synapse 30:255–262

    Article  CAS  PubMed  Google Scholar 

  • Heidbreder CA, Shippenberg TS (1994) U-69593 prevents cocaine sensitization by normalizing basal accumbens dopamine. Neuroreport 5:1797–1800

    Article  CAS  PubMed  Google Scholar 

  • Hurd YL, Kehr J, Ungerstedt U (1988) In vivo microdialysis as a technique to monitor drug transport: correlation of extracellular cocaine levels and dopamine overflow in the rat brain. J Neurochem 51:1314–1316

    Article  CAS  PubMed  Google Scholar 

  • Johanson CE, Fischman MW (1989) The pharmacology of cocaine related to its abuse. Pharmacol Rev 41:3–52

    CAS  PubMed  Google Scholar 

  • Johansson EK, Tucker SM, Ginn HB, Martin BR, Aceto MD (1992) Functional and dispositional tolerance develops during continuous cocaine exposure. Eur J Drug Metab Pharmacokinet 17:155–162

    Article  CAS  PubMed  Google Scholar 

  • Koob GF, Volkow ND (2010) Neurocircuitry of addiction. Neuropsychopharmacology 35:217–238

    Article  PubMed  Google Scholar 

  • Kreek MJ, Koob GF (1998) Drug dependence: stress and dysregulation of brain reward pathways. Drug Alcohol Depend 51:23–47

    Article  CAS  PubMed  Google Scholar 

  • Kuzmin AV, Gerrits MA, Van Ree JM (1998) Kappa-opioid receptor blockade with nor-binaltorphimine modulates cocaine self-administration in drug-naive rats. Eur J Pharmacol 358:197–202

    Article  CAS  PubMed  Google Scholar 

  • Kuzmin AV, Semenova S, Gerrits MA, Zvartau EE, Van Ree JM (1997) Kappa-opioid receptor agonist U50,488H modulates cocaine and morphine self-administration in drug-naive rats and mice. Eur J Pharmacol 321:265–271

    Article  CAS  PubMed  Google Scholar 

  • Land BB, Bruchas MR, Lemos JC, Xu M, Melief EJ, Chavkin C (2008) The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system. J Neurosci 28:407–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Logan RW, Williams WP 3rd, McClung CA (2014) Circadian rhythms and addiction: mechanistic insights and future directions. Behav Neurosci 128:387–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lynch WJ, Girgenti MJ, Breslin FJ, Newton SS, Taylor JR (2008) Gene profiling the response to repeated cocaine self-administration in dorsal striatum: a focus on circadian genes. Brain Res 1213:166–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maisonneuve IM, Archer S, Glick SD (1994) U50,488, a kappa opioid receptor agonist, attenuates cocaine-induced increases in extracellular dopamine in the nucleus accumbens of rats. Neurosci Lett 181:57–60

    Article  CAS  PubMed  Google Scholar 

  • Mantsch JR, Schlussman SD, Ho A, Kreek MJ (2000) Effects of cocaine self-administration on plasma corticosterone and prolactin in rats. J Pharmacol Exp Ther 294:239–247

    CAS  PubMed  Google Scholar 

  • Mantsch JR, Yuferov V, Mathieu-Kia AM, Ho A, Kreek MJ (2003) Neuroendocrine alterations in a high-dose, extended-access rat self-administration model of escalating cocaine use. Psychoneuroendocrinology 28:836–862

    Article  CAS  PubMed  Google Scholar 

  • Mantsch JR, Yuferov V, Mathieu-Kia AM, Ho A, Kreek MJ (2004) Effects of extended access to high versus low cocaine doses on self-administration, cocaine-induced reinstatement and brain mRNA levels in rats. Psychopharmacology 175:26–36

    Article  CAS  PubMed  Google Scholar 

  • Markou A, Koob GF (1991) Postcocaine anhedonia. An animal model of cocaine withdrawal. Neuropsychopharmacology 4:17–26

    CAS  PubMed  Google Scholar 

  • Marquez C, Nadal R, Armario A (2006) Influence of reactivity to novelty and anxiety on hypothalamic-pituitary-adrenal and prolactin responses to two different novel environments in adult male rats. Behav Brain Res 168:13–22

    Article  CAS  PubMed  Google Scholar 

  • Melief EJ, Miyatake M, Carroll FI, Beguin C, Carlezon WA Jr, Cohen BM, Grimwood S, Mitch CH, Rorick-Kehn L, Chavkin C (2011) Duration of action of a broad range of selective kappa-opioid receptor antagonists is positively correlated with c-Jun N-terminal kinase-1 activation. Mol Pharmacol 80:920–929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morris RW (1987) Circadian and circannual rhythms of emergency room drug-overdose admissions. Prog Clin Biol Res 227B:451–457

    CAS  PubMed  Google Scholar 

  • Mutschler NH, Covington Iii HE, Miczek KA (2001) Repeated self-administered cocaine "binges" in rats: effects on cocaine intake and withdrawal. Psychopharmacology 154:292–300

    Article  CAS  PubMed  Google Scholar 

  • Mutschler NH, Miczek KA (1998) Withdrawal from a self-administered or non-contingent cocaine binge: differences in ultrasonic distress vocalizations in rats. Psychopharmacology 136:402–408

    Article  CAS  PubMed  Google Scholar 

  • Nayak PK, Misra AL, Mule SJ (1976) Physiological disposition and biotransformation of (3H) cocaine in acutely and chronically treated rats. J Pharmacol Exp Ther 196:556–569

    CAS  PubMed  Google Scholar 

  • Parekh PK, Ozburn AR, McClung CA (2015) Circadian clock genes: effects on dopamine, reward and addiction. Alcohol 49:341–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pfeiffer A, Brantl V, Herz A, Emrich HM (1986) Psychotomimesis mediated by kappa opiate receptors. Science 233:774–776

    Article  CAS  PubMed  Google Scholar 

  • Picetti R, Ho A, Butelman ER, Kreek MJ (2010) Dose preference and dose escalation in extended-access cocaine self-administration in Fischer and Lewis rats. Psychopharmacology 211:313–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pottieger AE, Tressell PA, Surratt HL, Inciardi JA, Chitwood DD (1995) Drug use patterns of adult crack users in street versus residential treatment samples. J Psychoactive Drugs 27:27–38

    Article  CAS  PubMed  Google Scholar 

  • Reed B, Butelman ER, Fry RS, Kimani R, Kreek MJ (2018) Repeated administration of Opra Kappa (LY2456302), a novel, short-acting, selective KOP-r antagonist, in persons with and without cocaine dependence. Neuropsychopharmacology 43:928

    Article  PubMed  PubMed Central  Google Scholar 

  • Reed B, Fang N, Mayer-Blackwell B, Chen S, Yuferov V, Zhou Y, Kreek MJ (2012) Chromatin alterations in response to forced swimming underlie increased prodynorphin transcription. Neuroscience 220:109–118

    Article  CAS  PubMed  Google Scholar 

  • Resnick R, Fink M, Freedman AM (1974) High-dose cyclazocine therapy of opiate dependence. Am J Psychiatry 131:595–597

    Article  CAS  PubMed  Google Scholar 

  • Roberts DC, Andrews MM (1997) Baclofen suppression of cocaine self-administration: demonstration using a discrete trials procedure. Psychopharmacology 131:271–277

    Article  CAS  PubMed  Google Scholar 

  • Roberts DCS, Brebner K, Vincler M, Lynch WJ (2002) Patterns of cocaine self-administration in rats produced by various access conditions under a discrete trials procedure. Drug Alcohol Depend 67:291–299

    Article  CAS  PubMed  Google Scholar 

  • Rorick-Kehn LM, Witkin JM, Statnick MA, Eberle EL, McKinzie JH, Kahl SD, Forster BM, Wong CJ, Li X, Crile RS, Shaw DB, Sahr AE, Adams BL, Quimby SJ, Diaz N, Jimenez A, Pedregal C, Mitch CH, Knopp KL, Anderson WH, Cramer JW, McKinzie DL (2014) LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders. Neuropharmacology 77:131–144

    Article  CAS  PubMed  Google Scholar 

  • Schenk S, Partridge B, Shippenberg TS (1999) U69593, a kappa-opioid agonist, decreases cocaine self-administration and decreases cocaine-produced drug-seeking. Psychopharmacology 144:339–346

    Article  CAS  PubMed  Google Scholar 

  • Shippenberg TS, LeFevour A, Heidbreder C (1996) Kappa-opioid receptor agonists prevent sensitization to the conditioned rewarding effects of cocaine. J Pharmacol Exp Ther 276:545–554

    CAS  PubMed  Google Scholar 

  • Shippenberg TS, LeFevour A, Thompson AC (1998) Sensitization to the conditioned rewarding effects of morphine and cocaine: differential effects of the κ-opioid receptor agonist U69593. Eur J Pharmacol 345:27–34

    Article  CAS  PubMed  Google Scholar 

  • Sinha R, Garcia M, Paliwal P, Kreek MJ, Rounsaville BJ (2006) Stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes. Arch Gen Psychiatry 63:324–331

    Article  PubMed  Google Scholar 

  • Sivam SP (1989) Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism. J Pharmacol Exp Ther 250:818–824

    CAS  PubMed  Google Scholar 

  • Spangler R, Ho A, Zhou Y, Maggos CE, Yuferov V, Kreek MJ (1996) Regulation of kappa opioid receptor mRNA in the rat brain by ‘binge’ pattern cocaine administration and correlation with preprodynorphin mRNA. Mol Brain Res 38:71–76

    Article  CAS  PubMed  Google Scholar 

  • Todtenkopf MS, Marcus JF, Portoghese PS, Carlezon WA Jr (2004) Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats. Psychopharmacology 172:463–470

    Article  CAS  PubMed  Google Scholar 

  • Tornatzky W, Miczek KA (2000) Cocaine self-administration "binges": transition from behavioral and autonomic regulation toward homeostatic dysregulation in rats. Psychopharmacology 148:289–298

    Article  CAS  PubMed  Google Scholar 

  • Unterwald EM, Rubenfeld JM, Kreek MJ (1994) Repeated cocaine administration upregulates kappa and mu, but not delta, opioid receptors. Neuroreport 5:1613–1616

    Article  CAS  PubMed  Google Scholar 

  • Uz T, Akhisaroglu M, Ahmed R, Manev H (2003) The pineal gland is critical for circadian Period1 expression in the striatum and for circadian cocaine sensitization in mice. Neuropsychopharmacology 28:2117–2123

    Article  CAS  PubMed  Google Scholar 

  • Valenza M, Butelman ER, Kreek MJ (2017) Effects of the novel relatively short-acting kappa opioid receptor antagonist LY2444296 in behaviors observed after chronic extended-access cocaine self-administration in rats. Psychopharmacology 234:2219–2231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valenza M, Picetti R, Yuferov V, Butelman ER, Kreek MJ (2016) Strain and cocaine-induced differential opioid gene expression may predispose Lewis but not Fischer rats to escalate cocaine self-administration. Neuropharmacology 105:639–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Volkow ND, Koob GF, McLellan AT (2016) Neurobiologic advances from the brain disease model of addiction. N Engl J Med 374:363–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walsh S, Strain E, Abreu M, Bigelow G (2001) Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans. Psychopharmacology 157:151–162

    Article  CAS  PubMed  Google Scholar 

  • Ward AS, Haney M, Fischman MW, Foltin RW (1997) Binge cocaine self-administration in humans: intravenous cocaine. Psychopharmacology 132:375–381

    Article  CAS  PubMed  Google Scholar 

  • Weddington WW, Brown BS, Haertzen CA, Cone EJ, Dax EM, Herning RI, Michaelson BS (1990) Changes in mood, craving, and sleep during short-term abstinence reported by male cocaine addicts. A controlled, residential study. Arch Gen Psychiatry 47:861–868

    Article  CAS  PubMed  Google Scholar 

  • Wee S, Orio L, Ghirmai S, Cashman JR, Koob GF (2009) Inhibition of kappa opioid receptors attenuated increased cocaine intake in rats with extended access to cocaine. Psychopharmacology 205:565–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wee S, Specio SE, Koob GF (2007) Effects of dose and session duration on cocaine self-administration in rats. J Pharmacol Exp Ther 320:1134–1143

    Article  CAS  PubMed  Google Scholar 

  • Weiss F, Markou A, Lorang MT, Koob GF (1992) Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration. Brain Res 593:314–318

    Article  CAS  PubMed  Google Scholar 

  • Windisch KA, Kosobud AE, Czachowski CL (2014) Intravenous alcohol self-administration in the P rat. Alcohol 48:419–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zan GY, Wang Q, Wang YJ, Chen JC, Wu X, Yang CH, Chai JR, Li M, Liu Y, Hu XW, Shu XH, Liu JG (2016) p38 mitogen-activated protein kinase activation in amygdala mediates kappa opioid receptor agonist U50,488H-induced conditioned place aversion. Neuroscience 320:122–128

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Butelman ER, Schlussman SD, Ho A, Kreek MJ (2004) Effect of the endogenous kappa opioid agonist dynorphin A(1-17) on cocaine-evoked increases in striatal dopamine levels and cocaine-induced place preference in C57BL/6J mice. Psychopharmacology 172:422–429

    Article  CAS  PubMed  Google Scholar 

  • Zimmer BA, Dobrin CV, Roberts DC (2011) Brain-cocaine concentrations determine the dose self-administered by rats on a novel behaviorally dependent dosing schedule. Neuropsychopharmacology 36:2741–2749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zimmer BA, Dobrin CV, Roberts DC (2013) Examination of behavioral strategies regulating cocaine intake in rats. Psychopharmacology 225:935–944

    Article  CAS  PubMed  Google Scholar 

  • Zimmer BA, Roberts DC (2012) Cocaine self-administration in rats: hold-down procedures. Methods Mol Biol 829:279–290

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the valuable assistance from Dr. Linda Rorick-Kehn and thank Eli Lilly and Co. for providing the compound LY2540240 (LY2444296 hydrochloride), and Jeremy D Sherman for technical help.

Funding

This work was supported by The Dorothea Dix Fellowship Fund (MV), The Kopf Foundation Fellowship Fund (MV), The Gary R. Helman Postdoctoral Research Fellowship (KAW), the National Institute of Health grant R01 DA018151 (ERB), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (MJK).

Author information

Authors and Affiliations

  1. Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue - Box 171, New York, NY, 10065, USA

    Marta Valenza, Kyle A Windisch, Eduardo R. Butelman, Brian Reed & Mary Jeanne Kreek

Authors
  1. Marta Valenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyle A Windisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eduardo R. Butelman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Brian Reed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mary Jeanne Kreek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Marta Valenza or Kyle A Windisch.

Ethics declarations

All procedures adhered to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and the Principles of Laboratory Animal Care and were approved by the Institutional Animal Care and Use Committee of The Rockefeller University.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 54 kb)

ESM 2

(DOCX 1142 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Valenza, M., Windisch, K.A., Butelman, E.R. et al. Effects of Kappa opioid receptor blockade by LY2444296 HCl, a selective short-acting antagonist, during chronic extended access cocaine self-administration and re-exposure in rat. Psychopharmacology 237, 1147–1160 (2020). https://doi.org/10.1007/s00213-019-05444-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-019-05444-4

Keywords

Search

Navigation