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The role of prefrontal cortex D1-like and D2-like receptors in cocaine-seeking behavior in rats

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Abstract

Rationale

Evidence from preclinical and clinical studies indicates an important role for the mesocorticolimbic dopamine system in cocaine craving and relapse.

Objectives

To investigate the relative involvement of prefrontal cortex D1-like and D2-like dopamine receptors in cocaine-primed, drug-seeking behavior.

Methods

Rats were trained to press a lever to self-administer cocaine (i.v., 0.25 mg per infusion) in daily 2-h sessions. Responding was reinforced, contingent on a modified fixed-ratio 5 schedule. Reinstatement tests began after lever-pressing behavior was extinguished in the absence of cocaine and conditioned cues (light and tone). Before each reinstatement test, rats received bilateral microinfusions of different doses of selective D1-like and D2-like antagonists, SCH 23390, and eticlopride, respectively, followed by intraperitoneal administration of 10 mg/kg cocaine; 3 min later the session started. Responding in the reinstatement test was reinforced only by the conditioned cues contingent on a fixed-ratio 5 schedule.

Results

Both drugs dose dependently decreased cocaine-primed reinstatement without affecting operant behavior maintained by food. Eticlopride, but not SCH 23390, increased cocaine self-administration and decreased food-primed reinstatement at the dose found to decrease cocaine-primed reinstatement.

Conclusions

These data suggest that, although both D1-like and D2-like receptors in the prefrontal cortex are involved in cocaine-primed drug-seeking behavior, they may modulate different aspects of this process.

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Abbreviations

PFC:

Prefrontal cortex

ACC:

Anterior cingulate cortex

dPFC:

Dorsal prefrontal cortex

IL:

Infralimbic cortex

Cg1:

Cingulate cortex, area 1

TTX:

Tetrodotoxin

DA:

Dopamine

SA:

Self-administration

FR:

Fixed ratio

CS:

Conditioned stimuli

ICSA:

Intracerebral self-administration

PR:

Progressive ratio

References

  • Anderson SM, Bari AA, Pierce RC (2003) Administration of the D1-like dopamine receptor antagonist SCH-23390 into the medial nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug-seeking behavior in rats. Psychopharmacology 168:132–138

    Google Scholar 

  • Breiter HC, Gollub RL, Weisskoff RM, Kennedy DN, Makris N, Berke JD, Goodman JM, Kantor HL, Gastfriend DR, Riorden JP, Mathew RT, Rosen BR, Hyman SE (1997) Acute effects of cocaine on human brain activity and emotion. Neuron 19:591–611

    Article  CAS  PubMed  Google Scholar 

  • Caine SB, Koob GF (1994) Effects of dopamine D-1 and D-2 antagonists on cocaine self-administration under different schedules of reinforcement in the rat. J Pharmacol Exp Ther 270:209–218

    CAS  PubMed  Google Scholar 

  • Caine SB, Heinrichs SC, Coffin VL, Koob GF (1995) Effects of the dopamine D-1 antagonist SCH 23390 microinjected into the accumbens, amygdala or striatum on cocaine self-administration in the rat. Brain Res 692:47–56

    Article  CAS  PubMed  Google Scholar 

  • Caine SB, Negus SS, Mello NK, Bergman J (1999) Effects of dopamine D(1-like) and D(2-like) agonists in rats that self-administer cocaine. J Pharmacol Exp Ther 291:353–360

    CAS  PubMed  Google Scholar 

  • Caine SB, Negus SS, Mello NK (2000) Effects of dopamine D(1-like) and D(2-like) agonists on cocaine self-administration in rhesus monkeys: rapid assessment of cocaine dose-effect functions. Psychopharmacology 148:41–51

    Google Scholar 

  • Capriles N, Rodaros D, Sorge RE, Stewart J (2003) A role for the prefrontal cortex in stress- and cocaine-induced reinstatement of cocaine seeking in rats. Psychopharmacology 168:66–74

    Google Scholar 

  • Chausmer A, Ettenberg A (1999) Intraaccumbens raclopride attenuates amphetamine-induced locomotion, but fails to prevent the response-reinstating properties of food reinforcement. Pharmacol Biochem Behav 62:299–305

    Article  CAS  PubMed  Google Scholar 

  • Childress AR, Hole AV, Ehrman RN, Robbins SJ, McLellan AT, O’Brien CP (1993) Cue reactivity and cue reactivity interventions in drug dependence. NIDA Res Monogr 137:73–95

    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 

  • Ciccocioppo R, Sanna PP, Weiss F (2001) Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists. Proc Natl Acad Sci U S A 98:1976–1981

    Article  CAS  PubMed  Google Scholar 

  • Cornish JL, Kalivas PW (2000) Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction. J Neurosci 20:RC89

    CAS  PubMed  Google Scholar 

  • Epping-Jordan MP, Markou A, Koob GF (1998) The dopamine D-1 receptor antagonist SCH 23390 injected into the dorsolateral bed nucleus of the stria terminalis decreased cocaine reinforcement in the rat. Brain Res 784:105–115

    Article  CAS  PubMed  Google Scholar 

  • Fowler SC, Liou JR (1998) Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH 23390 do not. Psychopharmacology 140:81–90

    Google Scholar 

  • Gerdeman GL, Partridge JG, Lupica CR, Lovinger DM (2003) It could be habit forming: drugs of abuse and striatal synaptic plasticity. Trends Neurosci 26:184–192

    Article  CAS  PubMed  Google Scholar 

  • Goeders NE, Smith JE (1983) Cortical dopaminergic involvement in cocaine reinforcement. Science 221:773–775

    CAS  PubMed  Google Scholar 

  • Goeders NE, Smith JE (1986) Reinforcing properties of cocaine in the medical prefrontal cortex: primary action on presynaptic dopaminergic terminals. Pharmacol Biochem Behav 25:191–199

    Article  CAS  PubMed  Google Scholar 

  • Goeders NE, Dworkin SI, Smith JE (1986) Neuropharmacological assessment of cocaine self-administration into the medial prefrontal cortex. Pharmacol Biochem Behav 24:1429–1440

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Ito R, Robbins TW, Everitt BJ (2004) Differential control over cocaine-seeking behavior by nucleus accumbens core and shell. Nat Neurosci 7:389–397

    Article  CAS  PubMed  Google Scholar 

  • Jaffe JH, Cascella NG, Kumor KM, Sherer MA (1989) Cocaine-induced cocaine craving. Psychopharmacology 97:59–64

    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

    Google Scholar 

  • Kalivas PW, McFarland K (2003) Brain circuitry and the reinstatement of cocaine-seeking behavior. Psychopharmacology 168:44–56

    Google Scholar 

  • Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278:52–58

    Article  CAS  PubMed  Google Scholar 

  • Kosten TR, Rounsaville BJ, Kleber HD (1986) A 2.5-year follow-up of depression, life crises, and treatment effects on abstinence among opioid addicts. Arch Gen Psychiatry 43:733–738

    CAS  PubMed  Google Scholar 

  • Lee JH, Telang FW, Springer CS Jr, Volkow ND (2003) Abnormal brain activation to visual stimulation in cocaine abusers. Life Sci 73:1953–1961

    Article  CAS  PubMed  Google Scholar 

  • Leshner AI, Koob GF (1999) Drugs of abuse and the brain. Proc Assoc Am Physicians 111:99–108

    CAS  PubMed  Google Scholar 

  • McFarland K, Kalivas PW (2001) The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 21:8655–8663

    CAS  PubMed  Google Scholar 

  • McFarland K, Lapish CC, Kalivas PW (2003) Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 23:3531–3537

    CAS  PubMed  Google Scholar 

  • McGregor A, Roberts DC (1995) Effect of medial prefrontal cortex injections of SCH 23390 on intravenous cocaine self-administration under both a fixed and progressive ratio schedule of reinforcement. Behav Brain Res 67:75–80

    Article  CAS  PubMed  Google Scholar 

  • McGregor A, Baker G, Roberts DC (1996) Effect of 6-hydroxydopamine lesions of the medial prefrontal cortex on intravenous cocaine self-administration under a progressive ratio schedule of reinforcement. Pharmacol Biochem Behav 53:5–9

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin J, See RE (2003) Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats. Psychopharmacology 168:57–65

    Google Scholar 

  • Neisewander JL, Baker DA, Fuchs RA, Tran-Nguyen LT, Palmer A, Marshall JF (2000) Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment. J Neurosci 20:798–805

    CAS  PubMed  Google Scholar 

  • Nestler EJ, Aghajanian GK (1997) Molecular and cellular basis of addiction. Science 278:58–63

    Article  CAS  PubMed  Google Scholar 

  • Nowend KL, Arizzi M, Carlson BB, Salamone JD (2001) D1 or D2 antagonism in nucleus accumbens core or dorsomedial shell suppresses lever pressing for food but leads to compensatory increases in chow consumption. Pharmacol Biochem Behav 69:373–382

    Article  CAS  PubMed  Google Scholar 

  • Park WK, Bari AA, Jey AR, Anderson SM, Spealman RD, Rowlett JK, Pierce RC (2002) Cocaine administered into the medial prefrontal cortex reinstates cocaine-seeking behavior by increasing AMPA receptor-mediated glutamate transmission in the nucleus accumbens. J Neurosci 22:2916–2925

    CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic, San Diego

  • Ranaldi R, Wise RA (2001) Blockade of D1 dopamine receptors in the ventral tegmental area decreases cocaine reward: possible role for dendritically released dopamine. J Neurosci 21:5841–5846

    CAS  PubMed  Google Scholar 

  • Roberts AC, Wallis JD (2000) Inhibitory control and affective processing in the prefrontal cortex: neuropsychological studies in the common marmoset. Cereb Cortex 10:252–262

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Schenk S, Horger BA, Peltier R, Shelton K (1991) Supersensitivity to the reinforcing effects of cocaine following 6-hydroxydopamine lesions to the medial prefrontal cortex in rats. Brain Res 543:227–235

    Article  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

    Article  CAS  PubMed  Google Scholar 

  • Sun W, Rebec GV (2003) Lidocaine inactivation of ventral subiculum attenuates cocaine-seeking behavior in rats. J Neurosci 23:10258–10264

    CAS  PubMed  Google Scholar 

  • Thomas KL, Everitt BJ (2001) Limbic-cortical-ventral striatal activation during retrieval of a discrete cocaine-associated stimulus: a cellular imaging study with gamma protein kinase C expression. J Neurosci 21:2526–2535

    CAS  PubMed  Google Scholar 

  • Ushijima I, Carino MA, Horita A (1995) Involvement of D1 and D2 dopamine systems in the behavioral effects of cocaine in rats. Pharmacol Biochem Behav 52:737–741

    Article  CAS  PubMed  Google Scholar 

  • Weissenborn R, Robbins TW, Everitt BJ (1997) Effects of medial prefrontal or anterior cingulate cortex lesions on responding for cocaine under fixed-ratio and second-order schedules of reinforcement in rats. Psychopharmacology 134:242–257

    Google Scholar 

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Acknowledgments

We thank Adriana Thomas, Paul Langley and Faye Caylor for technical and administrative support. This research was supported by NIH (DA02451).

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Authors and Affiliations

  1. Program in Neural Science, Department of Psychology, Indiana University, 1101 E. 10th Street, Bloomington, IN 4740, USA

    WenLin Sun & George V. Rebec

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  1. WenLin Sun
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  2. George V. Rebec
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Correspondence to George V. Rebec.

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Sun, W., Rebec, G.V. The role of prefrontal cortex D1-like and D2-like receptors in cocaine-seeking behavior in rats. Psychopharmacology 177, 315–323 (2005). https://doi.org/10.1007/s00213-004-1956-x

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  • DOI: https://doi.org/10.1007/s00213-004-1956-x

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