Effect of dopamine receptor antagonists on renewal of cocaine seeking by reexposure to drug-associated contextual cues.
We recently found that in rats trained to self-administer a heroin-cocaine mixture, exposure to the drug self-administration environment, after extinction of the drug-reinforced behavior in a different context, leads to renewal of drug seeking. Here we further explored the role of contextual stimuli in drug seeking by characterizing the effect of drug-associated environmental stimuli on renewal of cocaine seeking. We also investigated whether activation of dopamine receptors contributes to context-induced renewal of cocaine seeking by testing the effects of selective D1-like (SCH 23390) and D2-like (raclopride) receptor antagonists. Rats were trained for 10 days to self-administer cocaine by pressing a lever. Next, lever pressing was extinguished in the presence of the discrete cues associated with cocaine infusions for 10 days in a context that was distinctively different from the drug-taking context. On the test days, rats were pretreated with SCH 23390 (0, 5 or 10 microg/kg) or raclopride (0, 50 or 100 microg/kg) and non-reinforced lever-pressing behavior was determined either in the extinction context (Control group) or the cocaine-associated context (Renewal group). Consistent with our previous report, cocaine seeking was renewed when rats were exposed to the drug-associated context after extinction in a different context. Furthermore, pretreatment with the D1-like or the D2-like receptor antagonists attenuated context-induced renewal of cocaine seeking. These data suggest that activation of dopamine receptors is involved in reinstatement of cocaine seeking induced by exposure to the drug self-administration context.
Crombag
Hans S
HS
Behavioral Neuroscience Branch, The National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, USA.
Grimm
Jeffrey W
JW
Shaham
Yavin
Y
D000818:Animals; D016739:Behavior, Addictive / Q000523:psychology; D003042:Cocaine / Q000494:pharmacology*; D003463:Cues; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D011954:Receptors, Dopamine / Q000502:physiology; D012646:Self Administration / Q000523:psychology
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D003042:Cocaine