Dopamine D1 receptor facilitation of depolarization-induced release of γ-amino-butyric acid in rat striatum is mediated by the cAMP/PKA pathway and involves P/Q-type calcium channels

• Published in: Synapse (New York, N.Y.) N.Y.), 2007-05, Vol.61 (5), p.310-319
• Main Authors: Arias-Montaño, J.-A., Floran, B., Floran, L., Aceves, J., Young, J.M.
• Format: Article
• Language: English
• Subjects: basal ganglia; dopamine D1 receptors; GABA; histamine H3 receptors; striatum; ω-agatoxin TK
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/syn.20372

Transmission in the “direct” pathway through the basal ganglia, which has an important role in the control of motor movement, is markedly facilitated by the concurrent activation of dopamine D1 receptors. Consistent with this, Ca2+‐dependent, depolarization‐induced release of [3H]‐GABA from striatal slices from rats pretreated with reserpine was greatly increased in the presence of 1 μM SKF 38393, a dopamine D1‐like receptor agonist. The effect of SKF 38393 was mimicked by 1 mM 8‐bromo‐cyclic AMP (Br‐cAMP) and inhibited by the protein kinase A (PKA) inhibitor H‐89, mean inhibition 92% ± 4% with 10 μM H‐89 (n = 3). The effects of SKF 38393 and Br‐cAMP were not additive. The stimulatory effects of SKF 38393 and Br‐cAMP were practically abolished in the presence of the histamine H3 receptor agonist immepip (1 μM). The depolarization‐induced release of [3H]‐GABA in the presence of SKF 38393 was not significantly inhibited by 5 μM nimodipine, an L‐type Ca2+ channel blocker, or by 0.3 μM ω‐conotoxin MVIIA, a selective blocker of N‐type channels. However, preincubation of the slices with 0.95 μM ω‐agatoxin TK, a P/Q‐type channel blocker, followed by washing before changing to a depolarizing medium containing SKF 38393, resulted in a marked inhibition of the stimulated release of [3H]‐GABA, mean 68% ± 4% (n = 3). These observations provide evidence that dopamine D1 agonist facilitation of the depolarization‐induced release of GABA from striatal terminals is mediated by the cAMP/PKA pathway and involves mainly P/Q‐type Ca2+ channels. Synapse 61:310–319, 2007. © 2007 Wiley‐Liss, Inc.