The role of prefrontal cortex D1-like and D2-like receptors in cocaine-seeking behavior in rats.
BACKGROUND
Evidence from preclinical and clinical studies indicates an important role for the mesocorticolimbic dopamine system in cocaine craving and relapse.


OBJECTIVE
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.
Program in Neural Science, Department of Psychology, Indiana University, 1101 E. 10th Street, Bloomington, IN 47405, USA.
WenLin
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Sun
George V
GV
Rebec
D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology*; D001552:Benzazepines / Q000008:administration & dosage / Q000493:pharmacokinetics; D003042:Cocaine / Q000008:administration & dosage / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005502:Food; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D008297:Male; D008845:Microinjections; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D012054:Reinforcement, Psychology; D012457:Salicylamides / Q000008:administration & dosage / Q000493:pharmacokinetics; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D013395:Sucrose; D003042:Cocaine; C045989:eticlopride