Interaction of taurine and related compounds with GABAergic neurones in the nucleus raphe dorsalis

Abstract

The effects of GABA A (muscimol) and GABA B (baclofen) receptor agonists on spontaneous motor activity and food consumption of rats were compared to those produced by taurine and related compounds (3-aminopropanesulphonic acid, 5-aminovaleric acid, and guanidinoethanesulphonic acid). Local application of muscimol into the nucleus raphe dorsalis caused a dose-dependent increase in spontaneous motor activity. Muscimol-stimulated motor activity was blocked by picrotoxin. High doses relative to muscimol of 3-aminopropanesulphonic acid, guanidinoethanesulphonic acid, and 5-aminovaleric acid also attenuated the action of muscimol. Taurine by itself was ineffective on locomotion but enhanced the effect of a small dose of muscimol. Baclofen also stimulated activity but to a lesser extent than muscimol. Baclofen's stimulatory action on motor activity was partially blocked by 5-aminovaleric acid, whereas 3-aminopropanesulphonic acid was without effect. Muscimol and baclofen both increased food consumption of rats. Picrotoxin blocked this effect of muscimol, whereas the action of baclofen was blocked by 5-aminovaleric acid. Muscimol, taurine, and guanidinoethanesulphonic acid all reduced 5-hydroxytryptamine (5-HT) concentration in the hypothalamus. In radioligand binding studies, guanidinoethanesulphonic acid at micromolar concentrations displaced [ 3H]GABA from GABA A receptors. It is concluded that taurine may have a slight direct effect on GABA receptors but is more likely to act as an indirect neuromodulator of GABAergic neurotransmission in the brain.