Drugs that decrease
drug-maintained responding at doses that do not decrease other behaviors in animals may be suitable candidates for development as medications to treat
drug abuse in humans. The present study examined whether this effect could be obtained with
phentermine, a
drug that has been reported to decrease
cocaine intake in humans. Rhesus monkeys were trained under multiple fixed-ratio 30-response schedules of food and i.v.
cocaine delivery.
Phentermine was always given as a slow, i.v. infusion. Acute treatment with
phentermine (0.3-10 mg/kg) decreased
cocaine-maintained responding at doses that did not decrease, or decreased less, food-maintained responding for each of three unit doses of
cocaine (10-100 microg/kg/injection). Subacute treatment with
phentermine (3 or 5.6 mg/kg, daily) also decreased
cocaine-maintained responding more than food-maintained responding. After subacute treatment was terminated, rates of
cocaine-maintained responding generally recovered to levels comparable to those seen during untreated control sessions.
Phentermine (0.3-3 mg/kg) did not generally increase responding associated with a very low (1 microg/kg/injection) unit dose of
cocaine, suggesting that the decrease in
cocaine-maintained responding at higher unit doses was not the result of a leftward shift in the
cocaine unit dose-effect function.
Phentermine (0.1-3 mg/kg) decreased responding maintained by 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl]
piperazine (
GBR 12909) (30 microg/kg/injection) at doses similar to those that decreased food-maintained responding. These results show that
phentermine is effective in decreasing
cocaine self-administration and suggest that it may be an effective medication for
cocaine abuse.