Modulation of endogenous GABA release by an antagonistic adenosine A1 / dopamine D1 receptor interaction in rat brain limbic regions but not basal ganglia
✍ Scribed by R. Dayne Mayfield; Brice A. Jones; Heather A. Miller; Johanna K. Simosky; Gaynor A. Larson; Nancy R. Zahniser
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 123 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0887-4476
No coin nor oath required. For personal study only.
✦ Synopsis
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.