GABAB receptor activation partially inhibits N-methyl-D-aspartate-mediated tyrosine hydroxylase stimulation in rat striatal slices

Abstract

The effect of the GABAB agonist, (+/-)-baclofen, on the N-methyl-D-aspartate (NMDA)-mediated stimulation of tyrosine hydroxylase activity was investigated in slices of rat striatum. Tyrosine hydroxylase activity was stimulated by NMDA in a concentration-dependent manner (EC50, 1.3 +/- 0.3 microM; maximum stimulation 194 +/- 7% of basal activity). The action of NMDA was reversed by the NMDA antagonist, 2-amino-5-phosphonovalerate (AP-5). (+/-)-Baclofen (100 microM) decreased the maximum effect of NMDA by 24 +/- 2% without significantly modifying its EC50. The IC50 for the inhibitory action of (+/-)-baclofen was 4.2 +/- 1.2 microM. These results show that GABAB receptor activation modulates NMDA-stimulated tyrosine hydroxylase activity, further supporting the possibility of a role of GABA in the regulation of striatal dopaminergic neurotransmission.