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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
Author(s) -
Mayfield R. Dayne,
Larson Gaynor,
Orona Richard A.,
Zahniser Nancy R.
Publication year - 1996
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199602)22:2<132::aid-syn6>3.0.co;2-e
Subject(s) - globus pallidus , adenosine a2a receptor , stimulation , medicine , receptor , dopamine receptor d2 , endocrinology , basal ganglia , medium spiny neuron , adenosine , dopamine , cgs 21680 , striatum , biology , adenosine receptor , agonist , chemistry , central nervous system
There is increasing evidence that adenosine (ADO) and dopamine (DA) interact directlyin 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 whichthese receptors modulate endogenous GABA release in discrete regions of the rat basalganglia and 2) whether GABA release is modulated by a direct and opposing interactionbetween ADO A 2a and DA D 2 receptors. Tissue slices ofstriatum (STR) containing globus pallidus (GP; STR/GP) and micropunches of STR, GP, andsubstantia nigra pars reticulata (SNr) were studied. Radioligand binding demonstrated thatADO A 1 , ADO A 2a , and DA D 2 receptors werepresent in each of the tissue preparations with the exception of SNr, in which ADOA 2a receptors were not detected. Stimulation of ADO A 2a receptors with CGS 21680 (1–10 nM) increased electrically stimulated GABA releasein 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) inhibitedevoked GABA release from STR/GP slices and both GP and SNr micropunches. TheD 2 ‐mediated inhibition of GABA release in GP was abolished in the presenceof CGS 21680 (10 nM). These experiments demonstrate that stimulation of ADOA 2a and DA D 2 receptors has opposing effects on endogenousGABA release in STR and GP. These opposing actions may explain the antagonisticinteractions between ADO and DA that have been observed in behavioral studies and supportthe hypothesis that the striatopallidal efferent system is an important anatomical substrate forthe A 2a /D 2 receptor interaction. © 1996 Wiley‐Liss,Inc.