Unique activation of extracellular striato-pallidal neurotransmitters in rats following acute risperidone

The present study investigated the effects of the putative atypical antipsychotic drug (APD), risperidone, on striatal monoamine and pallidal gamma-aminobutyric acid (GABA) function using dual probe in vivo microdialysis. 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-dihydroxyphenylacetic 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. Risperidone at the medium and high doses significantly reduced extracellular GABA levels in the GP. Simultaneous measurement of limb rigidity during microdialysis showed that risperidone dose-dependently produced significant increases in horizontal bar test catalepsy and fore- and hindlimb paw retraction latencies. The current results suggest novel effects of risperidone on striatal DA release, while the pallidal GABA changes are similar to previous results obtained with the atypical antipsychotic drug, clozapine. Additionally, the behavioral results predict the clinical expression of extrapyramidal motor side effects at high doses. Overall, these results support an atypical profile of risperidone when compared with typical APDs, yet one with unique neurochemical and behavioral properties.