Faculty Bibliography

1. The effects of cocaine (20 mg/kg s.c.) on 5-hydroxytryptamine (5-HT) turnover were examined in rats. 2. In vivo cocaine administration resulted in decreased turnover of 5-HT, as indicated by the decreased accumulation of 5-HT after pargyline administration and the decreased accumulation of 5-hydroxyindoleacetic acid (5-HIAA) following probenecid injection. 3. A time-related decrease in 5-HIAA concentrations and a small fall in 5-HT concentrations in the whole brain were observed following the acute administration of cocaine hydrochloride (20 mg/kg). Tryptophan levels were found to be slightly decreased in the brain. 4. Enhanced reactivity, but neither stereotypy nor hyperthermia, was observed following cocaine injection (20 mg/kg). 5. It is concluded that cocaine inhibits the turnover of brain 5-HT and that this action of cocaine may be responsible for the differences in a number of pharmacological effects between cocaine and amphetamine

In an attempt to identify specific binding to dopamine receptors the binding of 3H-pimozide to preparations of brain and to an artificial cellulose membrane was examined. Binding occurred rapidly, was pH and temperature dependent, and was displaceable by other neuroleptics. Displaceable binding was saturable at 5 X 10(-8) M pimozide. A weak correlation between IC50's for displacement of binding by drugs and their clinical potencies was observed. Displaceable binding of 3H-pimozide in different brain areas did not correlate with dopamine levels. The similarity of binding properties to brain and to artificial membrane suggests that these effects are a function of the physical-chemical properties of these drugs, and that these properties may be related to their clinical effect