Opposing actions of adenosine A2a and dopamine D2 receptor activation on GABA release in the basal ganglia: Evidence for an A2a/D2 receptor interaction in globus pallidus

✍ Scribed by R. Dayne Mayfield; Gaynor Larson; Richard A. Orona; Nancy R. Zahniser

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 858 KB
• Volume: 22
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199602)22:2<132::aid-syn6>3.0.co;2-e

✦ Synopsis

There is increasing evidence that adenosine (ADO) and dopamine (DA) interact directly in the basal ganglia via actions at ADO A,, and DA D2 receptors, respectively. The purpose of this study was to determine 1) the extent to which these receptors modulate endogenous GABA release in discrete regions of the rat basal ganglia and 2) whether GABA release is modulated by a direct and opposing interaction between ADO A,, and DA Dz receptors. Tissue slices of striatum (STR) containing globus pallidus (GP; STWGP) and micropunches of STR, GP, and substantia nigra pars reticulata (SNr) were studied. Radioligand binding demonstrated that ADO Al, ADO A,,, and DA D2 receptors were present in each of the tissue preparations with the exception of SNr, in which ADO Aza receptors were not detected. Stimulation of ADO A,, receptors with CGS 21680 (1-10 nM) increased electrically stimulated GABA release in STR/GP slices and GP micropunches. Consistent with the lack of A,, receptors in SNr, CGS 21680 had no effect on GABA release from this region. In contrast, stimulation of DA Dz receptors with N-0437 (1-100 nM) inhibited evoked GABA release from STWGP slices and both GP and SNr micropunches. The D,-mediated inhibition of GABA release in GP was abolished in the presence of CGS 21680 (10 nM). These experiments demonstrate that stimulation of ADO A,, and DA D2 receptors has opposing effects on endogenous GABA release in STR and GP. These opposing actions may explain the antagonistic interactions between ADO and DA that have been observed in behavioral studies and support the hypothesis that the striatopallidal efferent system is an important anatomical substrate for the A2,/D2 receptor interaction.