Brain region effects of clozapine on amino acid and monoamine transmission.

The purpose of the study was to compare the effects of clozapine and haloperidol on monoamine and amino acid transmission in limbic and extrapyramidal brain regions of the rat. In vivo microdialysis was used to measure the concentrations of neurotransmitters after acute and chronic drug administration. The acute administration of clozapine increased dopamine and glutamate in the medial prefrontal cortex and produced a greater increase, compared with haloperidol, in GABA (gamma-aminobutyric acid) efflux within the ventral pallidum. Chronic treatment with clozapine increased dopamine and serotonin in the medial prefrontal cortex. Chronic haloperidol administration increased glutamate in the striatum by fivefold whereas chronic clozapine treatment had no effect on striatal glutamate. Furthermore, chronic haloperidol administration transiently increased, then decreased, GABA efflux in the substantia nigra. Overall, clozapine has a preferential effect on mesocorticolimbic neurotransmission whereas haloperidol alters glutamate and GABA efflux within the extrapyramidal motor system.