Characterization of dopamine D1 and D2 receptor function in socially housed cynomolgus monkeys self-administering cocaine.
BACKGROUND
Social rank has been shown to influence dopamine (DA) D(2) receptor function and vulnerability to cocaine self-administration in cynomolgus monkeys. The present studies were designed to extend these findings to maintenance of cocaine reinforcement and to DA D(1) receptors.


OBJECTIVE
Examine the effects of a high-efficacy D(1) agonist on an unconditioned behavior (eyeblinking) and a low-efficacy D(1) agonist on cocaine self-administration, as well as the effects of cocaine exposure on D(2) receptor function across social ranks, as determined by positron emission tomography (PET).


METHODS
Effects of the high-efficacy D(1) agonist SKF 81297 and cocaine (0.3-3.0 mg/kg) on spontaneous blinking were characterized in eight monkeys during 15-min observation periods. Next, the ability of the low-efficacy D(1) agonist SKF 38393 (0.1-17 mg/kg) to decrease cocaine self-administration (0.003-0.1 mg/kg per injection, IV) was assessed in 11 monkeys responding under a fixed-ratio 50 schedule. Finally, D(2) receptor levels in the caudate and putamen were assessed in nineteen monkeys using PET.


RESULTS
SKF 81297, but not cocaine, significantly increased blinking in all monkeys, with slightly greater potency in dominant monkeys. SKF 38393 dose-dependently decreased cocaine-maintained response rates with similar behavioral potency and efficacy across social rank. After an extensive cocaine self-administration history, D(2) receptor levels did not differ across social ranks.


CONCLUSIONS
These results suggest that D(1) receptor function is not substantially influenced by social rank in monkeys from well-established social groups. While an earlier study showed that dominant monkeys had higher D(2) receptor levels and were less sensitive to the reinforcing effects of cocaine during initial exposure, the present findings indicate that long-term cocaine use changed D(2) receptor levels such that D(2) receptor function and cocaine reinforcement were not different between social ranks. These findings suggest that cocaine exposure attenuated the impact of social housing on DA receptor function.
Czoty
Paul W
PW
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA.
Morgan
Drake
D
Shannon
Erin E
EE
Gage
H Donald
HD
Nader
Michael A
MA
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000493:pharmacokinetics; D001552:Benzazepines / Q000494:pharmacology; D001767:Blinking / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006608:Hierarchy, Social; D008252:Macaca fascicularis; D008297:Male; D017072:Neostriatum / Q000000981:diagnostic imaging; D010880:Piperidines / Q000493:pharmacokinetics; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012646:Self Administration; D014018:Tissue Distribution / Q000187:drug effects; D014055:Tomography, Emission-Computed / Q000379:methods
D001549:Benzamides; D001552:Benzazepines; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D010880:Piperidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C083673:fluoroclebopride; C067113:SK&F 81297; D003042:Cocaine