Psychopharmacology

, Volume 177, Issue 3, pp 315–323 | Cite as

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

Original Investigation

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.

Keywords

Cocaine Self-administration Reinstatement Conditioned stimuli Prefrontal cortex Mesocorticolimbic circuitry SCH 23390 Eticlopride 

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

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Program in Neural Science, Department of PsychologyIndiana UniversityBloomingtonUSA

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