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A role for the prefrontal cortex in stress- and cocaine-induced reinstatement of cocaine seeking in rats

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Abstract

Rationale and objective.

It is well established that stress induces reinstatement of drug seeking in an animal model of relapse. Here we studied the role of the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) in foot-shock stress-induced reinstatement of cocaine seeking.

Methods.

Groups of rats were trained to self-administer cocaine (0.5 mg/kg per infusion, i.v., 3 h/day for 9 days) and after ten drug-free days were exposed to extinction and reinstatement test sessions. Each 60 min of extinction was separated by a 30-min time-out period after which the lever and stimulus lights were reintroduced. Rats were given four 1-h extinction sessions on day 1 and then on subsequent days were given two to three 1-h extinction sessions that were followed by a 3-h test for reinstatement. Tests were run every 48 h. In one set of experiments, the effects of inactivation of the prelimbic (PL), infralimbic (IL) or OFC by tetrodotoxin (TTX, 5 ng/0.5 µl per side) on reinstatement induced by foot shock (5 min, intermittent, 1 mA) or priming injections of cocaine (20 mg/kg, i.p.) were determined. In a second set, the effects of infusions of the D1-like and D2-like dopamine receptor antagonists (SCH 23390 and raclopride) were studied using the same methods.

Results.

TTX infusions into the PL cortex blocked both foot shock and cocaine-induced reinstatement. TTX into OFC attenuated foot-shock-induced, but not cocaine-induced reinstatement. Infusions into IL were ineffective. Infusions of SCH 22390 (0.25 µg/0.5 µl per side) into either PL or OFC blocked foot-shock-induced reinstatement, but infusions into PL had no effect on cocaine-induced reinstatement. Raclopride (5 µg/0.5 µl per side) had no effect on foot-shock-induced reinstatement in either PL or OFC or on cocaine-induced reinstatement when infused into PL. Neither TTX nor SCH23390 infusions into PL or OFC had any effect on lever pressing for sucrose.

Conclusions.

These results suggest that the PL and OFC regions form part of the circuitry mediating the effects of foot shock stress on reinstatement of drug seeking and that the PL region may be a common pathway for cue, drug and foot-shock stress-induced reinstatement of drug seeking.

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Acknowledgements.

We thank Francesco Leri for his help with the study on sucrose reinforcement. Supported by grants from the National Institute of Drug Abuse (USA) and Fonds pour la Formation de Chercheurs et l'Aide à la Recherche du Québec (FCAR).

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Authors and Affiliations

  1. Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, 1455 de Maisonneuve Blvd., Montreal, Quebec, Canada H3G 1M8, Canada

    Nancy Capriles, Demetra Rodaros, Robert E. Sorge & Jane Stewart

  2. Mental Health Research Institute, University of Michigan, 205 Zina, Pitcher Place, MI 48109-0720, USA, USA

    Nancy Capriles

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  1. Nancy Capriles
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  2. Demetra Rodaros
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  3. Robert E. Sorge
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  4. Jane Stewart
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Correspondence to Jane Stewart.

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Capriles, N., Rodaros, D., Sorge, R.E. et al. A role for the prefrontal cortex in stress- and cocaine-induced reinstatement of cocaine seeking in rats. Psychopharmacology 168, 66–74 (2003). https://doi.org/10.1007/s00213-002-1283-z

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  • DOI: https://doi.org/10.1007/s00213-002-1283-z

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