Modulation of endogenous GABA release by an antagonistic adenosine A(1)/dopamine D-1 receptor interaction in rat brain limbic regions but not basal ganglia

Behavioral and biochemical studies suggest that a negative interaction exis ts between adenosine A(1) and dopamine D-1 receptors in the brain and that this may contribute to the psychomotor effects of adenosine receptor agonis ts and antagonists. We examined the functional significance of A(1) and D-1 receptor subtypes in modulating electrically evoked endogenous GABA releas e from slices/punches of rat basal ganglia (striatum, globus pallidus, stri atum containing globus pallidus, and substantia nigra reticulata) and limbi c regions (ventral pallidum and nucleus accumbens). In basal ganglia, stimu lation of A(1) receptors with the selective agonist R-PIA(1-100 nM) resulte d in a concentration-dependent decrease in GABA release. The selective A(1) antagonist DPCPX (10-100 nM) increased GABA release, suggesting that endog enous adenosine tonically inhibits GABA release. However, in basal ganglia, consistent dopamine D-1 receptor modulation of GABA, release was not observ ed in response to either D-1 agonists or antagonists. Furthermore, the A(1) receptor-mediated inhibition of GABA release was not changed by concurrent activation of D-1 receptors, thus confirming the lack of D-1 receptor modu lation under these conditions. In contrast, in ventral pallidum and nucleus accumbens, stimulation of D-1 receptors with SKF-82958 (1 mu M) increased GABA release significantly. The D-1 receptor-mediated increase in GABA rele ase was attenuated by concurrent activation of adenosine A(1) receptors. Th ese results are consistent with the hypothesis that an antagonistic A(1)/D- 1 receptor interaction may be important in modulating GABA release in limbi c regions. Synapse 33:274-281, 1999.;I 1999 Wiley-Liss, Inc.