Blockade or stimulation of D1 dopamine receptors attenuates cue reinstatement of extinguished cocaine-seeking behavior in rats

• Published in: Psychopharmacologia 2002, Vol.159 (3), p.284-293
• Main Authors: ALLEWEIRELDT, Andrea T, WEBER, Suzanne M, KIRSCHNER, Kenneth F, BULLOCK, Breanna L, NEISEWANDER, Janet L
• Format: Article
• Language: English
• Subjects: Agonists; Animals; Behavior, Addictive; Benzazepines - pharmacology; Biological and medical sciences; Cocaine; Cocaine - pharmacology; Cues; Dopamine; Dopamine Agonists - pharmacology; Dopamine Antagonists - pharmacology; Dopamine D1 receptors; Dopamine Uptake Inhibitors - pharmacology; Dose-Response Relationship, Drug; Drug abuse; Drug addiction; Drug addictions; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Grooming; Grooming - drug effects; Grooming - physiology; Latency; Male; Medical sciences; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1 - agonists; Receptors, Dopamine D1 - antagonists & inhibitors; Receptors, Dopamine D1 - physiology; Reinstatement; Stereotyped behavior; Stereotyped Behavior - drug effects; Stereotyped Behavior - physiology; Toxicology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130100904

D(1) dopamine receptor antagonists and agonists attenuate cocaine reinstatement of cocaine-seeking behavior (i.e., responding in the absence of cocaine reinforcement). The present study investigated the effects of a D(1) antagonist (SCH-23390), partial agonist (SKF-38393), and full agonist (SKF-81297) on reinstatement of cocaine-seeking behavior elicited by presentation of cocaine-paired cues. Rats that had been trained to self-administer cocaine with a light/tone stimulus complex paired with each infusion underwent extinction across days. After responding diminished, rats were given response-contingent access to the cocaine-paired stimulus complex. The effects of SCH-23390 (0-10.0 microg/kg), SKF-38393 (0-3.0 mg/kg), and SKF-81297 (0-3.0 mg/kg) on cue reinstatement of cocaine-seeking behavior were examined. The ability of the two D(1) agonists to independently reinstate cocaine-seeking behavior and the effects of SKF-81297 on cocaine reinstatement were also examined. To investigate the possibility of behavioral interference, the effects of SKF-38393 and SKF-81297 on grooming and stereotypy were assessed. SCH-23390 and SKF-81297, but not SKF-38393, attenuated cue reinstatement. However, while SKF-81297 dose-dependently increased response latency, SCH-23390 did not. SKF-81297 also independently reinstated responding at the two lowest doses tested while SKF-38393 had no effect. Furthermore, SKF-81297 decreased cocaine reinstatement and increased response latency only at the highest dose. Finally, stereotypy was observed at all doses of SKF-81297 that also decreased responding, although the patterns of changes in these behaviors did not completely correspond. While the antagonist and full agonist produced similar effects on cocaine-seeking behavior, only the agonist increased response latency, suggesting that different processes mediate the effects of these drugs.