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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
Author(s) -
Mayfield R. Dayne,
Jones Brice A.,
Miller Heather A.,
Simosky Johanna K.,
Larson Gaynor A.,
Zahniser Nancy R.
Publication year - 1999
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(19990915)33:4<274::aid-syn4>3.0.co;2-3
Subject(s) - globus pallidus , nucleus accumbens , basal ganglia , dopamine , medicine , dopamine receptor d1 , endocrinology , ventral pallidum , neuroscience , chemistry , striatum , adenosine , substantia nigra , agonist , adenosine a2a receptor , dopamine receptor , dopamine receptor d2 , adenosine a1 receptor , biology , adenosine receptor , receptor , dopaminergic , central nervous system
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 μM) 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. Synapse 33:274–281, 1999. © 1999 Wiley‐Liss, Inc.