Skip to main content

Advertisement

SpringerLink
Log in

Repeated nicotine exposure enhances responding with conditioned reinforcement

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

Abstract

Rationale

Stimuli associated with a reinforcer (e.g., an addictive drug) can acquire conditioned reinforcing effects. Clinical observations indicate that smoking depends strongly upon conditioned reinforcement (i.e., cues support smoking behavior); however, little is known about the effects of repeated nicotine exposure on these processes.

Objective

This study investigated the consequences of prior repeated nicotine exposure on responding with conditioned reinforcement and on the potentiation of conditioned reinforcement by intra-NAc amphetamine infusion.

Methods

Rats received repeated saline or nicotine injections (0.35 mg/kg; 15 days) and were, following 3 days of withdrawal, trained to associate a tone + light stimulus with water reinforcement for 10 days. Animals were subsequently tested on acquisition of a new instrumental response with conditioned reinforcement (i.e., 14 days after the final nicotine injection). In additional experiments, animals received an infusion of amphetamine (10 µg per side) prior to the conditioned reinforcement test.

Results

Prior repeated nicotine exposure produced a behaviorally specific enhancement of responding with conditioned reinforcement. Furthermore, repeated nicotine pretreatment also augmented the potentiation of conditioned reinforcement by intra-NAc amphetamine.

Conclusions

These findings demonstrate that prior repeated nicotine exposure augments the control over behavior by a conditioned reinforcer. Such long-lasting alterations in incentive motivational processes produced by repeated nicotine exposure may depend on drug-induced neuroadaptations in dopamine-regulated signaling within limbic-striatal brain regions that could underly persistent and compulsive aspects of addiction.

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

  • Balfour DJ, Benwell ME, Birrell CE, Kelly RJ, Al-Aloul M (1998) Sensitization of the mesoaccumbens dopamine response to nicotine. Pharmacol Biochem Behav 59:1021–1030

    CAS  PubMed  Google Scholar 

  • Balfour DJ, Wright AE, Benwell ME, Birrell CE (2000) The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence. Behav Brain Res 113:73–83

    CAS  PubMed  Google Scholar 

  • Berke JD, Hyman SE (2000) Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25:515–532

    CAS  PubMed  Google Scholar 

  • Birrell CE, Balfour DJ (1998) The influence of nicotine pretreatment on mesoaccumbens dopamine overflow and locomotor responses to d-amphetamine. Psychopharmacology 140:142–149

    Google Scholar 

  • Cador M, Taylor JR, Robbins TW (1991) Potentiation of the effects of reward-related stimuli by dopaminergic-dependent mechanisms in the nucleus accumbens. Psychopharmacology 104:377–385

    CAS  PubMed  Google Scholar 

  • Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, Hoffman A, Perkins KA, Sved AF (2001) Cue dependency of nicotine self-administration and smoking. Pharmacol Biochem Behav 70:515–530

    CAS  PubMed  Google Scholar 

  • Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, Hoffman A, Perkins KA (2002) Environmental stimuli promote the acquisition of nicotine self-administration in rats. Psychopharmacology 163:230–237

    Article  CAS  PubMed  Google Scholar 

  • Carter BL, Tiffany ST (1999) Meta-analysis of cue-reactivity in addiction research. Addiction 94:327–340

    CAS  PubMed  Google Scholar 

  • Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O’Brien CP (1999) Limbic activation during cue-induced cocaine craving. Am J Psychiatry 156:11–18

    CAS  PubMed  Google Scholar 

  • Cunningham ST, Kelley AE (1992) Opiate infusion into nucleus accumbens: contrasting effects on motor activity and responding for conditioned reward. Brain Res 588:104–114

    CAS  PubMed  Google Scholar 

  • Deroche-Gamonet V, Piat F, Le Moal M, Piazza PV (2002) Influence of cue-conditioning on acquisition, maintenance and relapse of cocaine intravenous self-administration. Eur J Neurosci 15:1363–1370

    PubMed  Google Scholar 

  • Di Chiara G (1999) Drug addiction as dopamine-dependent associative learning disorder. Eur J Pharmacol 375:13–30

    PubMed  Google Scholar 

  • Dols M, Willems B, van den Hout M, Bittoun R (2000) Smokers can learn to influence their urge to smoke. Addict Behav 25:103–108

    Article  CAS  PubMed  Google Scholar 

  • Due DL, Huettel SA, Hall WG, Rubin DC (2002) Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging. Am J Psychiatry 159:954–960

    Article  PubMed  Google Scholar 

  • Everitt BJ, Robbins TW (1992) Amygdala-ventral striatal interactions in reward-related processes. In: Aggelton JP (ed) The amygdala. Wiley, New York, pp 401–409

  • Everitt BJ, Wolf ME (2002) Psychomotor stimulant addiction: a neural systems perspective. J Neurosci 22:3312–3320

    CAS  PubMed  Google Scholar 

  • Everitt BJ, Dickinson A, Robbins TW (2001) The neuropsychological basis of addictive behaviour. Brain Res Brain Res Rev 36:129–138

    Article  CAS  PubMed  Google Scholar 

  • Grant S, London ED, Newlin DB, Villemagne VL, Liu X, Contoreggi C et al (1996) Activation of memory circuits during cue-elicited cocaine craving. Proc Nat Acad Sci U S A 93:12040–12045

    CAS  Google Scholar 

  • Hill RT (1970) Facilitation of conditioned reinforcement as a mechanism of psychomotor stimulation. In: Costa E, Garattini S (eds) International symposium on amphetamines and related compounds. Raven Press, New York, pp 781–795

  • Horger BA, Shelton K, Schenk S (1990) Preexposure sensitizes rats to the rewarding effects of cocaine. Pharmacol Biochem Behav 37:707–711

    CAS  PubMed  Google Scholar 

  • Horger BA, Giles MK, Schenk S (1992) Preexposure to amphetamine and nicotine predisposes rats to self-administer a low dose of cocaine. Psychopharmacology 107:271–276

    CAS  PubMed  Google Scholar 

  • Hyman SE, Malenka RC (2001) Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci 2:695–703

    Article  CAS  PubMed  Google Scholar 

  • Jentsch JD, Taylor JR (1999) Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology 146:373–390

    CAS  PubMed  Google Scholar 

  • Jentsch JD, Taylor JR (2001) Impaired inhibition of conditioned responses produced by subchronic administration of phencyclidine to rats. Neuropsychopharmacology 24:66–74

    Article  CAS  PubMed  Google Scholar 

  • Kelley AE, Delfs JM (1991a) Dopamine and conditioned reinforcement. I. Differential effects of amphetamine microinjections into striatal subregions. Psychopharmacology 103:187–196

    CAS  PubMed  Google Scholar 

  • Kelley AE, Delfs JM (1991b) Dopamine and conditioned reinforcement. II. Contrasting effects of amphetamine microinjection into the nucleus accumbens with peptide microinjection into the ventral tegmental area. Psychopharmacology 103:197–203

    CAS  PubMed  Google Scholar 

  • Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24:97–129

    CAS  PubMed  Google Scholar 

  • Lett BT (1989) Repeated exposures intensify rather than diminish the rewarding effects of amphetamine, morphine, and cocaine. Psychopharmacology 98:357–362

    CAS  PubMed  Google Scholar 

  • Mucha RF, Pauli P, Angrilli A (1998) Conditioned responses elicited by experimentally produced cues for smoking. Can J Physiol Pharmacol 76:259–268

    Article  CAS  PubMed  Google Scholar 

  • Mucha RF, Geier A, Pauli P (1999) Modulation of craving by cues having differential overlap with pharmacological effect: evidence for cue approach in smokers and social drinkers. Psychopharmacology 147:306–313

    Article  CAS  PubMed  Google Scholar 

  • Nestler EJ (2001) Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2:119–128

    CAS  PubMed  Google Scholar 

  • Niaura R, Abrams D, Demuth B, Pinto R, Monti P (1989) Responses to smoking-related stimuli and early relapse to smoking. Addict Behav 14:419–428

    CAS  PubMed  Google Scholar 

  • Norrholm SD, Bibb JA, Nestler EJ, Ouimet CC, Taylor JR, Greengard P (2003) Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5. Neuroscience 116:19–22

    Article  CAS  PubMed  Google Scholar 

  • O’Brien CP, Childress AR, Ehrman R, Robbins SJ (1998) Conditioning factors in drug abuse: can they explain compulsion? J Psychopharmacol 12:15–22

    CAS  PubMed  Google Scholar 

  • Olausson P, Engel JA, Söderpalm B (1999) Behavioral sensitization to nicotine is associated with behavioral disinhibition: counteraction by citalopram. Psychopharmacology 142:111–119

    Google Scholar 

  • Olausson P, Åkesson P, Petersson A, Engel JA, Söderpalm B (2001) Behavioral and neurochemical consequences of repeated nicotine treatment in the serotonin-depleted rat. Psychopharmacology 155:348–361

    Article  CAS  PubMed  Google Scholar 

  • Olausson P, Jentsch JD, Taylor JR (2003) Repeated nicotine exposure enhances reward-related learning in the rat. Neuropsychopharmacology 28:1264–1271

    Article  CAS  PubMed  Google Scholar 

  • Parkinson JA, Olmstead MC, Burns LH, Robbins TW, Everitt BJ (1999) Dissociations in effects of lesions of the nucleus accumbens core and shell on appetitive pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by D-amphetamine. J Neurosci 19:2401–2411

    CAS  PubMed  Google Scholar 

  • Parsons LH, Justice JB Jr (1993) Serotonin and dopamine sensitization in the nucleus accumbens, ventral tegmental area, and dorsal raphe nucleus following repeated cocaine administration. J Neurochem 61:1611–1619

    CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, Sydney

  • Phillips GD, Robbins TW, Everitt BJ (1994) Mesoaccumbens dopamine-opiate interactions in the control over behaviour by a conditioned reinforcer. Psychopharmacology 114:345–359

    CAS  PubMed  Google Scholar 

  • Piazza PV, Deminiere JM, le Moal M, Simon H (1990) Stress- and pharmacologically induced behavioral sensitization increases vulnerability to acquisition of amphetamine self-administration. Brain Res 514:22–26

    CAS  PubMed  Google Scholar 

  • Picciotto MR, Corrigall WA (2002) Neuronal systems underlying behaviors related to nicotine addiction: neural circuits and molecular genetics. J Neurosci 22:3338–3341

    CAS  PubMed  Google Scholar 

  • Pierce RC, Kalivas PW (1997) A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Brain Res Rev 25:192–216

    CAS  PubMed  Google Scholar 

  • Reid MS, Mickalian JD, Delucchi KL, Hall SM, Berger SP (1998) An acute dose of nicotine enhances cue-induced cocaine craving. Drug Alcohol Depend 49:95–104

    CAS  PubMed  Google Scholar 

  • Reid MS, Mickalian JD, Delucchi KL, Berger SP (1999) A nicotine antagonist, mecamylamine, reduces cue-induced cocaine craving in cocaine-dependent subjects. Neuropsychopharmacology 20:297–307

    CAS  PubMed  Google Scholar 

  • Robbins TW, Everitt BJ (1999) Drug addiction: bad habits add up. Nature 398:567–570

    CAS  PubMed  Google Scholar 

  • Robbins TW, Watson BA, Gaskin M, Ennis C (1983) Contrasting interactions of pipradrol, d-amphetamine, cocaine, cocaine analogues, apomorphine and other drugs with conditioned reinforcement. Psychopharmacology 80:113–119

    CAS  PubMed  Google Scholar 

  • Robbins TW, Cador M, Taylor JR, Everitt BJ (1989) Limbic-striatal interactions in reward-related processes. Neurosci Biobehav Rev 13:155–162

    CAS  PubMed  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18:247–291

    CAS  PubMed  Google Scholar 

  • Robinson TE, Berridge KC (2003) Addiction. Annu Rev Psychol 54:25–53

    Article  PubMed  Google Scholar 

  • Robinson TE, Kolb B (1997) Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine. J Neurosci 17:8491–8497

    CAS  PubMed  Google Scholar 

  • Robinson TE, Kolb B (1999) Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine. Eur J Neurosci 11:1598–1604

    CAS  PubMed  Google Scholar 

  • Rose JE, Levin ED (1991) Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking. Br J Addict 86:605–609

    CAS  PubMed  Google Scholar 

  • Schenk S, Partridge B (2001) Influence of a conditioned light stimulus on cocaine self-administration in rats. Psychopharmacology 154:390–396

    CAS  PubMed  Google Scholar 

  • See RE (2002) Neural substrates of conditioned-cued relapse to drug-seeking behavior. Pharmacol Biochem Behav 71:517–529

    CAS  PubMed  Google Scholar 

  • Shahan TA, Bickel WK, Madden GJ, Badger GJ (1999) Comparing the reinforcing efficacy of nicotine containing and de-nicotinized cigarettes: a behavioral economic analysis. Psychopharmacology 147:210–216

    CAS  PubMed  Google Scholar 

  • Shalev U, Grimm JW, Shaham Y (2002) Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev 54:1–42

    PubMed  Google Scholar 

  • Shippenberg TS, Heidbreder C (1995) Sensitization to the conditioned rewarding effects of cocaine: pharmacological and temporal characteristics. J Pharmacol Exp Ther 273:808–815

    CAS  PubMed  Google Scholar 

  • Taylor JR, Horger BA (1999) Enhanced responding for conditioned reward produced by intra-accumbens amphetamine is potentiated after cocaine sensitization. Psychopharmacology 142:31–40

    CAS  PubMed  Google Scholar 

  • Taylor JR, Robbins TW (1984) Enhanced behavioral control by conditioned reinforcers following microinjections of D-amphetamine into the nucleus accumbens. Psychopharmacology 84:405–412

    CAS  PubMed  Google Scholar 

  • Taylor JR, Robbins TW (1986) 6-Hydroxydopamine lesions of the nucleus accumbens, but not of the caudate nucleus, attenuate enhanced responding with reward-related stimuli produced by intra-accumbens D-amphetamine. Psychopharmacology 90:390–397

    CAS  PubMed  Google Scholar 

  • Tiffany ST, Carter BL (1998) Is craving the source of compulsive drug use? J Psychopharmacol 12:23–30

    Google Scholar 

  • Volkow ND, Fowler JS (2000) Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb Cortex 10:318–325

    CAS  PubMed  Google Scholar 

  • Wolf ME, White FJ, Nassar R, Brooderson RJ, Khansa MR (1993) Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization. J Pharmacol Exp Ther 264:249–255

    CAS  PubMed  Google Scholar 

  • Wyvell CL, Berridge KC (2001) Incentive sensitization by previous amphetamine exposure: increased cue-triggered “wanting” for sucrose reward. J Neurosci 21:7831–7840

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the valuable technical assistance of Ms. Victoria Stewart and Ms. Valyphone Phantarangsy. The present study was supported by PHS grant (DA 11717) to J.R.T., a Fredrik & Inger Thuring’s Foundation award to P.O. and a pilot project grant from the Yale TTURC (DA 13334). P.O. was the recipient of a post-doctoral fellowship from the Swedish Brain Foundation.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Laboratory of Molecular Psychiatry, Yale University, 34 Park Street, New Haven, CT 06508, USA

    Peter Olausson & Jane R. Taylor

  2. Department of Psychology, UCLA, 1285 Franz Hall, Los Angeles, CA 90095, USA

    J. David Jentsch

Authors
  1. Peter Olausson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. David Jentsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jane R. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jane R. Taylor.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Olausson, P., Jentsch, J.D. & Taylor, J.R. Repeated nicotine exposure enhances responding with conditioned reinforcement. Psychopharmacology 173, 98–104 (2004). https://doi.org/10.1007/s00213-003-1702-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-003-1702-9

Keywords

Search

Navigation