The dopamine D3 receptor partial agonist CJB 090 inhibits the discriminative stimulus but not the reinforcing or priming effects of cocaine in squirrel monkeys.
BACKGROUND
Dopamine D3 receptor mechanisms have been implicated in the abuse-related behavioral effects of cocaine.


OBJECTIVE
The purpose of this study was to investigate the effects of the D3 receptor partial agonist CJB 090 on the discriminative stimulus, reinforcing and priming effects of cocaine in squirrel monkeys. Complementary studies were conducted to compare CJB 090's effects on food-maintained behavior and species-typical unconditioned behaviors.


METHODS
Monkeys were trained to: (1) discriminate cocaine from saline using a two-lever choice procedure, (2) self-administer cocaine on a second-order fixed-interval, fixed-ratio schedule of i.v. drug injection, or (3) self-administer food on a comparable second-order schedule of food delivery. A final group of monkeys served in quantitative observational studies of unconditioned behaviors.


RESULTS
In cocaine discrimination studies, pretreatment with CJB 090 significantly attenuated cocaine's discriminative stimulus effects. CJB 090 also significantly attenuated the partial cocaine-like stimulus effects of the preferential D3 receptor agonist PD 128907 but not the preferential D2 receptor agonist sumanirole. CJB 090 did not attenuate either self-administration of cocaine or cocaine-induced reinstatement of extinguished drug-seeking at a dose that reduced responding maintained by food. CJB 090 did not induce scratching or biting (species-typical effects of D2/3 receptor agonists) or catalepsy (typical effect of D2/3 receptor antagonists).


CONCLUSIONS
The results provide no evidence that CJB 090 reduced either the reinforcing or priming effects of cocaine but do suggest that CJB 090, acting via a D3 receptor mechanism, antagonized the discriminative stimulus effects of cocaine at a dose that did not induce adverse side effects.
Achat-Mendes
Cindy
C
Division of Neuroscience, New England Primate Research Center, Harvard Medical School, One Pine Hill Dr., P.O. Box 9102, Southborough, MA 01772, USA. Cindy_Achat-Mendes@hms.harvard.edu
Platt
Donna M
DM
Newman
Amy H
AH
Spealman
Roger D
RD
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003213:Conditioning, Psychological / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D008297:Male; D010078:Oxazines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D012054:Reinforcement, Psychology; D012453:Saimiri; D012646:Self Administration
D001549:Benzamides; D001562:Benzimidazoles; D001578:Benzopyrans; D018491:Dopamine Agonists; C545833:N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide; D010078:Oxazines; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; C108539:U 95666E; D003042:Cocaine