Is in vivo striatal acetylcholine output under a tonic inhibitory control by dopamine?
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 by depletion of dopamine stores after 5 mg/kg reserpine + 150 mg/kg alpha-methyltyrosine. Treatment with SCH 39166 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.
Imperato
A
A
G.M. Everett Laboratory of Neuropsychopharmacology, Department of Neuroscience Bernard B. Brodie, University of Cagliari, Italy.
Obinu
M C
MC
Gessa
G L
GL
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012016:Reference Values
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000109:Acetylcholine; D004298:Dopamine