The effects of antipsychotics on the turnover rate of GABA and acetylcholine in rat brain nuclei.

Abstract

SEVERAL lines of indirect evidence indicate that the nigrostriatal and mesolimbic dopaminergic systems interact with acetylcholine (ACh)1,2,3 and γ-aminobutyric acid4 (GABA)-secreting neurones. The reciprocal relationships among these neurones have not, however, been established with precision. Nucleus caudatus and nucleus accumbens are innervated by dopaminergic axons which have their cell bodies located in substantia nigra and ventral tegmental area5, respectively. These nuclei contain high concentrations of ACh6 and GABA7 and a high activity of cholineacetyltransferase (CAT)6 and glutamic acid decarboxylase7 (GAD). The nucleus accumbens and nucleus caudatus are connected with globus pallidus and substantia nigra which also contain GABA7, ACh6 and their synthesising enzymes. Antipsychotics, including chlorpromazine, clozapine and haloperidol increase the turnover rate of dopamine (DA) in the nucleus caudatus and nucleus accumbens8. Clozapine, a non-cataleptogenic antipsychotic, preferentially increases the DA turnover in the nucleus accumbens whereas chlorpromazine and haloperidol, two cataleptogenic antipsychotics show a preferential effect on the nucleus caudatus8.