UNIQUE ACTIVATION OF EXTRACELLULAR STRIATOPALLIDAL NEUROTRANSMITTERS IN RATS FOLLOWING ACUTE RISPERIDONE

The present study investigated the effects of the putative atypical an tipsychotic drug (APD), risperidone, on striatal monoamine and pallida l gamma-aminobutyric acid (GABA) function using dual probe in vivo mic rodialysis. Risperidone (0.03, 0.3, 3 mg/kg) or vehicle was injected ( s.c.) into female, Sprague-Dawley rats fitted with dual microdialysis probes in the striatum and the globus pallidus (GP). In the striatum, risperidone increased extracellular levels of dopamine (DA) and 3,4-di hydroxyphenylacetic acid (DOPAC) at all doses and the serotonin (5-HT) metabolite, 5-hydroxyindoleacetic acid (5-HIAA), at the highest dose. The increase in striatal DA was most pronounced at the lowest dose of risperidone; however, DOPAC showed a dose dependent increase. Risperi done at the medium and high doses significantly reduced extracellular GABA levels in the GP. Simultaneous measurement of limb rigidity durin g microdialysis showed that risperidone dose-dependently produced sign ificant increases in horizontal bar test catalepsy and fore- and hindl imb paw retraction latencies. The current results suggest novel effect s of risperidone on striatal DA release, while the pallidal GABA chang es are similar to previous results obtained with the atypical antipsyc hotic drug, clozapine. Additionally, the behavioral results predict th e clinical expression of extrapyramidal motor side effects at high dos es. Overall, these results support an atypical profile of risperidone when compared with typical APDs, yet one with unique neurochemical and behavioral properties. (C) 1998 Elsevier Science B.V. All rights rese rved.