Discriminative stimulus effects of cocaine in squirrel monkeys: lack of antagonism by the dopamine D2 partial agonists terguride, SDZ 208-911, and SDZ 208-912.
The effects of cocaine alone and after pretreatment with the dopamine D2 partial agonists terguride, SDZ 208-911, and SDZ 208-912 were determined in squirrel monkeys trained to discriminate cocaine from saline using a two-lever drug discrimination procedure. When tested alone, cocaine engendered dose-related increases in the percentage of responses on the cocaine-associated lever, reaching virtually exclusive cocaine-appropriate responding after a dose of 1.0 mg/kg. Pretreatment with terguride (0.003-0.03 mg/kg), SDZ 208-911 (0.001-0.01), and SDZ 208-912 (0.003-0.018 mg/kg) did not consistently alter the discriminative stimulus effects of cocaine. Although some doses of each D2 partial agonist either increased (notably SDZ 208-911) or decreased (notably SDZ 208-912) the level of cocaine-appropriate responding engendered by low to intermediate doses of cocaine, none of the drugs reduced the percentage of cocaine-appropriate responding engendered by low to intermediate doses of cocaine, none of the drugs reduced the percentage of cocaine-appropriate responses engendered by 1.0 mg/kg cocaine. The results do not support the view that terguride, SDZ 208-911, or SDZ 208-912 would serve as functional antagonists of the subjective effects of cocaine.
Spealman
R D
RD
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772-9102, USA.
D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D008090:Lisuride / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012453:Saimiri
D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; C062737:N-(2,6-dimethylergoline-8-yl)-2,2-dimethylpropanamide; C059362:N-(2-chloro-6-methylergoline-8-yl)-2,2-dimethylpropanamide; C006208:dironyl; D008090:Lisuride; D003042:Cocaine