Differential influence of GABA-ergic agents on dopamine metabolism in extrapyramidal and limbic systems of the rat

Abstract

The effect of GABA receptor agonists (muscimol, SL 76002) and GABA transaminase inhibitors (e.g. dipropylacetamide) on dopamine (DA) metabolism has been investigated in striatum and limbic areas of the rat. SL 76002, muscimol and dipropylacetamide decrease the rate of DA disappearance after α-methyl-p-tyrosine in striatum but not in limbic areas (nucleus accumbens+olfactory tubercle). Moreover, SL 76002 and muscimol reduce more markedly in striatum than in limbic areas the synthesis of DA as estimated from the in vivo accumulation of DOPA following inhibition of dopadecarboxylase or the in vitro formation of 14CO 2 from 1- 14C-tyrosine (in slices). However, SL 76002 and muscimol counteract in a dose-dependent manner haloperidol-induced increase in DA utilization and in tyrosine hydroxylase activity in both striatum and limbic areas, this effect being more pronounced in the former region. These findings indicate that GABA mimetic agents affect more markedly striatal than limbic DA neurons suggesting a more effective GABA-ergic influence on the extrapyramidal than on the limbic DA systems.