Role of cholinergic system in modulating gamma‐aminobutyric acid and dopamine functions in rat brain

Abstract

AbstractThe effects of cholinergic and anticholinergic agents on dopamine (DA) and gamma‐aminobutyric acid (GABA) levels in specific rat brain regions were studied. A single injection of physostigmine (2 mg/kg, i.p.) produced no significant effect on the levels of DA and GABA in corpus stritum. Treatment with atropine increased striatal GABA content by 38%, suggesting that decreased cholinergic activity alters the release of GABA. Administration of physostigmine partially antagonized the atropine‐induced rise in GABA level of corpus striatum, indicating that the cholinomimetic agent facilitated GABA release in this region. This increase in GABA content is not associated with any change in DA content in the striatum. To further assess the effect of physostigmine on GABA level, animals were pretreated with amino‐oxyacetic acid (AOAA), an inhibitor of the GABA‐degrading enzyme 4‐aminobutyrate 2‐oxoglutarate transaminase (GAGA‐T). Treatment with AOAA (50 mg/kg) elevated GABA levels in corpus striatum, midbrain, and frontal cortex. In contrast, DA levels were decreased by 25% and 30% in the frontal cortex and corpus striatum, respectively. Administration of physostigmine facilitated GABA release in AOAA‐treated animals resulting in a 16% lowering of GABA levels in striatum. Physostigmine did not change striatal DA in rats pretreated with AOAA. These results suggest that cholinergic interneurons in striatum probably facilitate the functioning of GABAergic neurons, which elicit inhibitory effects on the DA system. The clinical importance of such an interneuronal circuit is discussed.