Effects of selective dopamine D1 and D2 receptor agonists on the rate of GABA synthesis in mouse brain

The effects of dopamine D1 and D2 receptor agonists and antagonists on the rate of GABA synthesis in four regions of mouse brain (corpus striatum, cerebellum, cortex and hippocampus) were examined after irreversible inhibition of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T) by gabaculine. The dopamine D2 receptor agonists PPHT, LY 171555 and RU 24213 exerted a dose-related inhibitory effect on GABA synthesis in these four regions. The decreases in the rate of GABA formation were prevented by the dopamine D2 receptor antagonist S(-)-sulpiride. The dopamine D1 receptor agonists SKF 77434 and SKF 38393 augmented gabaculine-induced GABA accumulation in the corpus striatum only, and this effect was blocked by the dopamine D1 receptor antagonist SCH 23390. However, SKF 81297 and SKF 82958, two other dopamine D1 receptor agonists, did not affect or only marginally altered the rate of GABA synthesis. Stimulation of D2 receptors thus induces a decrease in the rate of GABA formation in the four brain areas examined, whereas stimulation of D1 receptors either increases GABA synthesis in the corpus striatum or does not alter it. This effect appears to be independent of the degree of receptor occupancy.