Modulation of endogenous GABA release by an antagonistic adenosine A1/dopamineD1 receptor interaction in rat brain limbic regions but not basal ganglia

Abstract

Behavioral and biochemical studies suggest that a negative interaction exists between adenosine A(1) and dopamine D(1) receptors in the brain and that this may contribute to the psychomotor effects of adenosine receptor agonists and antagonists. We examined the functional significance of A(1) and D(1) receptor subtypes in modulating electrically evoked endogenous GABA release from slices/punches of rat basal ganglia (striatum, globus pallidus, striatum containing globus pallidus, and substantia nigra reticulata) and limbic regions (ventral pallidum and nucleus accumbens). In basal ganglia, stimulation of A(1) receptors with the selective agonist R-PIA (1-100 nM) resulted in a concentration-dependent decrease in GABA release. The selective A(1) antagonist DPCPX (10-100 nM) increased GABA release, suggesting that endogenous adenosine tonically inhibits GABA release. However, in basal ganglia, consistent dopamine D(1) receptor modulation of GABA, release was not observed 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 modulation under these conditions. In contrast, in ventral pallidum and nucleus accumbens, stimulation of D(1) receptors with SKF-82958 (1 microM) increased GABA release significantly. The D(1) receptor-mediated increase in GABA release was attenuated by concurrent activation of adenosine A(1) receptors. These results are consistent with the hypothesis that an antagonistic A(1)/D(1) receptor interaction may be important in modulating GABA release in limbic regions.