OPPOSING ACTIONS OF ADENOSINE-A(2A) AND DOPAMINE-D-2 RECEPTOR ACTIVATION ON GABA RELEASE IN THE BASAL GANGLIA - EVIDENCE FOR AN A(2A) D-2 RECEPTOR INTERACTION IN GLOBUS-PALLIDUS/

There is increasing evidence that adenosine (ADO) and dopamine (DA) in teract directly in the basal ganglia via actions at ADO A(2a) and DA D -2 receptors, respectively. The purpose of this study was to determine 1) the extent to which these receptors modulate endogenous GABA relea se in discrete regions of the rat basal ganglia and 2) whether GABA re lease is modulated by a direct and opposing interaction between ADO A( 2a), and DA D-2 receptors. Tissue slices of striatum (STR) containing globus pallidus (GP; STR/GP) and micropunches of STR, GP, and substant ia nigra pars reticulata (SNr) were studied. Radioligand binding demon strated that ADO A(1), ADO A(2a), and DA D-2 receptors were present in each of the tissue preparations with the exception of SNr, in which A DO A(2a) receptors were not detected. Stimulation of ADO A(2a) recepto rs with CGS 21680 (1-10 nM) increased electrically stimulated GABA rel ease in STR/GP slices and GP micropunches. Consistent with the lack of A(2a) receptors in SNr, CGS 21680 had no effect on GABA release from this region. In contrast, stimulation of DA D-2 receptors with N-0437 (1-100 nM) inhibited evoked GABA release from STR/GP slices and both G P and SNr micropunches. The D-2-mediated inhibition of GABA release in GP was abolished in the presence of CGS 21680 (10 nM). These experime nts demonstrate that stimulation of ADO A(2a) and DA D-2 receptors has opposing effects on endogenous GABA release in STR and GP. These oppo sing actions may explain the antagonistic interactions between ADO and DA that have been observed in behavioral studies and support the hypo thesis that the striatopallidal efferent system is an important anatom ical substrate for the A(2a)/D-2 receptor interaction. (C) 1996 Wiley- Liss, Inc.