Does dopamine exert a tonic inhibitory control on the release of striatal acetylcholine in vivo?
The role of dopamine transmission on striatal acetylcholine release was investigated by using brain microdialysis. Blockade of dopamine D2 receptors with (-)-sulpiride or haloperidol increased acetylcholine release to a maximum of 80% (after 50 and 0.5 mg/kg, respectively). This effect was prevented by blockade of dopamine D1 receptors with 0.5 mg/kg SCH 39166 or 0.1 mg/kg SCH 23390, or by depletion of dopamine stores after 5 mg/kg reserpine + 150 mg/kg alpha-methyltyrosine. Treatment with SCH 39166, SCH 23390 or reserpine + alpha-methyltyrosine reduced acetylcholine release by about a maximum of 30%. Stimulation of dopamine D2 receptors with LY 171555 (quinpirole) at a low, sedative dose (0.05 mg/kg) reduced acetylcholine release by about 30% with no further reduction at higher doses up to 1 mg/kg. Moreover, LY 171555 (0.1 mg/kg) given to SCH 39166 (0.5 mg/kg)- or SKF 38393 (20 mg/kg)-pretreated rats did not decrease acetylcholine release, suggesting that its effect is through a dopamine D1 receptor-mediated mechanism. In contrast, in dopamine-depleted rats, LY 171555 0.1 mg/kg became more effective in decreasing acetylcholine release (about 70%) also after SCH 39166 (0.5 mg/kg) pretreatment (about 80%), thus acting independently of dopamine D1 receptor mechanisms. These results indicate that, in normal circumstances, endogenous dopamine facilitates striatal acetylcholine release through dopamine D1 receptors. The results argue against the commonly accepted view that dopamine D2 receptors exert a tonic inhibitory control on acetylcholine release. Moreover, they suggest that dopamine D2 receptors, in circumstances of dopamine depletion, may exert an inhibitory control on acetylcholine release independent of dopamine D1 receptor mechanisms.
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Bernard B. Brodie' Department of Neuroscience, University of Cagliari, Italy.
Obinu
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Dazzi
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Gessa
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D000109:Acetylcholine / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013268:Stimulation, Chemical
D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000109:Acetylcholine; D004298:Dopamine