Lack of effects of apomorphine, haloperidol and clozapine on the synthesis and utilization of brain GABA

Abstract

The synthesis of GABA was studied as the accumulation of GABA following inhibition of the GABA-α-ketoglutaric acid aminotransferase byγ-acetylenic GABA (GAG) orγ-vinyl GABA. The disappearance of GABA was studied by means of inhibition of glutamate decarboxylase by 4-deoxypyridoxine. Systemic administration of the dopamine receptor agonist apomorphine did not change the accumulation or the disappearance of GABA in the substantia nigra and the corpus striatum of the rat. However, a very high dose of apomorphine somewhat increased the GAG-induced GABA accumulation in the corpus striatum. The dopamine receptor antagonists haloperidol and clozapine did not modify the accumulation and disappearance of GABA in the two structures, except for a slight decrease in the GAG-induced GABA accumulation in the substantia nigra. Following an acute hemisection, the neural connections between the substantia nigra and the corpus striatum are interrupted on one side of the brain. Apomorphine did not influence the accumulation or the disappearance of GABA in the substantia nigra and in the corpus striatum on the sectioned side of the brain. These results indicate that the synthesis and the utilization of GABA in the two structures studied are not influenced to any greater extent by changes in dopamine receptor activity.