A pharmacological analysis of the discriminative stimulus properties of d-amphetamine in rhesus monkeys.
Rhesus monkeys (n = 4) were trained to discriminate d-amphetamine (AMPH; 0.67 or 1.33 mumol/kg i.v.) from saline in a two lever, food-reinforced drug discrimination paradigm. After acquisition of the discrimination (average, 127 sessions), the monkeys were tested with a series of compounds selected to characterize the neuronal mechanism(s) of the discrimination. AMPH (0.08-2.6 mumol/kg), cocaine (0.06-1.0 mumol/kg; n = 4), the dopamine (DA) uptake inhibitor bupropion (0.25-2.0 mumol/kg; n = 2) and the norepinephrine (NE) uptake inhibitor nisoxetine (1.0-16 mumol/kg; n = 4) produced dose-related increases in the percentage of responses that occurred on the AMPH-appropriate lever during test sessions in all monkeys tested. For all other drugs tested, individual differences in effects were noted. Compounds with primarily D2 DA receptor activity, including apomorphine (0.06-1.0 mumol/kg; n = 4), piribedil (0.25-8.0 mumol/kg; n = 4), bromocriptine (0.12-1.0 mumol/kg; n = 4) and propylbutyldopamine (0.25-4.0 mumol/kg; n = 3) occasioned AMPH-appropriate responding in one or two monkeys. The D1 agonist SKF 38393 (0.5-64 mumol/kg; n = 4) and pentobarbital (4.0-32 mumol/kg; n = 4) substituted for AMPH in only one monkey. In tests for antagonism, the D1 antagonist SCH 23390 (0.015-0.03 mumol/kg; n = 2) blocked completely the discriminative stimulus effects of AMPH in a dose-related manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Kamien
J B
JB
Department of Pharmacological & Physiological Sciences, Pritzker School of Medicine, University of Chicago, Illinois.
Woolverton
W L
WL
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000502:physiology
D001552:Benzazepines; D011954:Receptors, Dopamine; D010868:Pimozide; D003042:Cocaine; D001058:Apomorphine; D003913:Dextroamphetamine; D011224:Prazosin; D010646:Phentolamine