DIFFERENTIAL-EFFECTS OF UNIQUE PROFILE ANTIPSYCHOTIC-DRUGS ON EXTRACELLULAR AMINO-ACIDS IN THE VENTRAL PALLIDUM AND GLOBUS-PALLIDUS OF RATS

The effects of antipsychotic drugs (APDs) on brain dopamine receptors in the striatum are ultimately expressed through efferent projections which primarily use aminoacid transmitters, including gamma-aminobutyr ic acid and glutamate. The present study examined the effects of APDs on Extracellular amino acid levels in the rat ventral pallidum (VP) an d globus pallidus (GP), areas that receive projections from distinct s triatal subregions. Clozapine, an APD with low motor side effect liabi lity, and metoclopramide, a low-potency APD with high motor side effec t liability, were compared with haloperidol, a widely used APD with hi gh motor side effect liability. Drugs were administered subcutaneously and amino acid levels were monitored concurrently in the VP and GP by intracranial microdialysis, High doses of haloperidol and metoclopram ide increased and clozapine decreased extracellular gamma-aminobutyric acid levels in the GP but not the VP. Low, but not high, doses of the three drugs tended to increase extracellular glutamate levels in both pallidal regions. Clozapine, but not the other two drugs, decreased e xtracellular threonine in the GP and glycine and threonine in the VP. Results indicate a correlation between increased gamma-aminobutyric ac id levels in the GP and the propensity of the APDs tested to induce mo tor side effects. The novel effects of clozapine on extracellular glyc ine and threonine further distinguish this drug as a unique antipsycho tic compound.