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Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys.
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1989
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The study compares cocaine self‑administration with that of several monoamine uptake inhibitors that also displace cocaine binding sites. Squirrel monkeys were trained on a second‑order fixed‑interval schedule of intravenous drug injection, and dose‑effect curves were generated by measuring stable response rates across saline and multiple drug doses. Cocaine and the tested monoamine uptake inhibitors produced similar self‑administration rates, whereas mazindol was effective in only half the subjects; potency rankings matched those for [3H]cocaine displacement, indicating that reinforcing effects are mediated by specific brain recognition sites.
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.