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[Effect of ATP-sensitive K+ channel blocker (quinine) on the dopamine decrease induced by selective D3 agonist
K Shimizu1, M Watanabe, Y Kodama
1Department of Psychiatry, National Defense Medical College, 3-2, Namiki, Tokorozawa, 359-8513 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi = Japanese Journal of Psychopharmacology
|January 19, 2002
Summary
Dopamine D3 receptors in rat striatum regulate dopamine release via ATP-sensitive K+ channels. Blocking these channels with quinine reversed the inhibitory effects of a D3 agonist, suggesting a novel feedback mechanism.
Area of Science:
- Neuroscience
- Pharmacology
- Neurochemistry
Background:
- Dopamine D3 receptors are implicated in regulating dopamine release.
- Autoregulation of dopamine release is crucial for maintaining dopaminergic system balance.
- The precise mechanisms of D3 receptor-mediated dopamine autoregulation are not fully elucidated.
Purpose of the Study:
- To investigate the role of dopamine D3 receptors in dopamine auto-regulated systems in the rat striatum.
- To explore the involvement of ATP-sensitive K+ (KATP) channels in D3 receptor-mediated dopamine regulation.
Main Methods:
- In vivo brain microdialysis in rats.
- Local infusion of the D3 receptor agonist 7-OH-DPAT into the striatum.
- Local application of the KATP channel blocker quinine.
Main Results:
- Dopamine D3 receptor agonist 7-OH-DPAT decreased extracellular dopamine levels.
- KATP channel blocker quinine dose-dependently increased extracellular dopamine levels.
- Quinine blocked the 7-OH-DPAT-induced decrease in dopamine, suggesting KATP channel involvement.
Conclusions:
- Dopamine D3 receptors likely act as presynaptic autoreceptors or in a short-loop negative feedback system in the striatum.
- KATP channels are suggested to be present in nigrostriatal dopaminergic terminals.
- Dopamine release is tonically inhibited by D3 autoreceptors/feedback systems via KATP channel activation.