Endogenous dopamine facilitates striatal in vivo acetylcholine release by acting on D1 receptors localized in the striatum.
Intrastriatal application of the D1 antagonist SCH 23390 by two procedures, reverse dialysis (20 microM) and local injection (0.45 nmol per striatum), elicited a reduction in acetylcholine (ACh) release superimposable on that induced by systemic administration. The novel selective D1 antagonist SCH 39166 produced a similar decreasing effect on striatal ACh release on local injection (0.45 nmol per striatum). On the other hand, local application of SCH 23390 into the frontal cortices (0.45 nmol per side) failed to alter striatal ACh overflow, indicating that the drug does not diffuse out of its injection site to any significant extent. The dopamine release inducer d-amphetamine (2 mg/kg s.c.) and the dopamine uptake inhibitor cocaine raised ACh release like the D1 agonists. These effects were completely blocked by 10 microM SCH 23390 applied by reverse dialysis. The results suggest that D1 receptors regulating ACh release are located in the striatum.
Consolo
S
S
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Girotti
P
P
Russi
G
G
Di Chiara
G
G
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D005260:Female; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1 / Q000378:metabolism / Q000502:physiology*
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D003042:Cocaine; D000109:Acetylcholine; D003913:Dextroamphetamine; D004298:Dopamine