Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys.
The self-administration of cocaine was compared with that of bupropion, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine, mazindol, methylphenidate and nomifensine, drugs that displace [3H]cocaine from its binding sites and have monoamine uptake inhibiting effects in common with those of cocaine. Squirrel monkeys responded under a second-order fixed-interval schedule of consequent i.v. drug injection, and dose-effect curves were established by determining stable rates of responding maintained by saline and a range of doses of each drug. Cocaine (0.01-0.56 mg/kg/injection), bupropion (0.1-3.0 mg/kg/injection), 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3- phenylpropyl)piperazine-(0.03-1.0 mg/kg/injection), methylphenidate (0.01-0.3 mg/kg/injection) and nomifensine (0.01-0.3 mg/kg) maintained comparable rates and patterns of responding in all subjects, whereas mazindol (0.03-0.3 mg/kg) maintained self-administration behavior in only half the monkeys studied. The present results in conjunction with those of previous studies in squirrel monkeys reveal a close correspondence between the relative potencies of cocaine and related drugs for maintaining i.v. self-administration and for increasing rates of schedule-controlled responding, suggesting that the reinforcing and psychomotor-stimulant effects of the drugs are mediated similarly. The potency relations observed in the present study also agree generally with those observed for displacement of specifically bound [3H]cocaine in monkey caudate-putamen suggesting that the reinforcing effects of cocaine involve its actions at specific recognition sites in brain.
Bergman
J
J
Department of Psychiatry, Harvard Medical School, New England Regional Primate Research Center, Southborough, Massachusetts.
Madras
B K
BK
Johnson
S E
SE
Spealman
R D
RD
D000818:Animals; D016642:Bupropion; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D008297:Male; D008454:Mazindol / Q000494:pharmacology; D008774:Methylphenidate / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009627:Nomifensine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology; D012453:Saimiri; D012646:Self Administration
D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D011427:Propiophenones; D016642:Bupropion; D009627:Nomifensine; D008774:Methylphenidate; C043425:vanoxerine; D008454:Mazindol; D003042:Cocaine; D004298:Dopamine