D1-receptor drugs and cocaine-seeking behavior: investigation of receptor mediation and behavioral disruption in rats.
BACKGROUND
Dopamine D1-receptor antagonists and agonists both attenuate cocaine-seeking behavior (i.e., operant responding in the absence of cocaine reinforcement) elicited by a cocaine prime or cocaine-paired stimuli. It remains unclear whether these effects are D1-receptor mediated.


OBJECTIVE
The present study tested whether a D1 antagonist (SCH-23390) would reverse the attenuating effects of a D1 agonist (SKF-81297) on cocaine-seeking behavior and whether behavioral disruption is involved in these effects.


METHODS
Rats trained to press a lever for cocaine reinforcement with light and tone cues paired with each infusion underwent daily extinction sessions during which responding had no scheduled consequences (i.e., neither cocaine nor the cocaine-paired stimulus complex was available). After responding diminished, the effects of the D1 antagonist on the dose-response functions of the D1 agonist for reinstatement of cocaine-seeking behavior by response-contingent cue presentations or cocaine priming were examined. A separate experiment assessed the effects of the agonist on the dose-response function of the antagonist for cue reinstatement. Stereotyped behavior and activity were also measured during each test session.


RESULTS
The attenuating effects of SKF-81297 on cocaine-seeking behavior during cocaine-primed reinstatement were reversed by co-administration of SCH-23390. However, no evidence for reversal of the attenuation during cue reinstatement was found even though agonist-induced stereotypy and antagonist-induced hypoactivity were reversed by co-administration of the two drugs during the same test session.


CONCLUSIONS
The findings suggest that the attenuating effects of D1-receptor drugs on cocaine-seeking behavior during cocaine reinstatement are mediated by dopamine D1 receptors; however, it remains unclear whether the effects of these drugs on cocaine-seeking behavior during cue reinstatement are D1-receptor mediated. Nevertheless, it is evident that the attenuation of cocaine-seeking behavior by these drugs is not simply due to behavioral disruption.
Alleweireldt
Andrea T
AT
Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, USA, USA.
Kirschner
Kenneth F
KF
Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, USA, USA.
Blake
Camille B
CB
Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, USA, USA.
Neisewander
Janet L
JL
Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, USA, USA. janet.neisewander@asu.edu.
D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy; D003042:Cocaine / Q000008:administration & dosage; D003463:Cues; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D003042:Cocaine