Blockade of muscarinic receptors potentiates D1 dependent turning behavior and c-fos expression in 6-hydroxydopamine-lesioned rats but does not influence D2 mediated responses.
In rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal pathway, blockade of muscarinic receptors by scopolamine potentiates the contralateral turning induced by selective dopaminergic D1 agonists (SKF 38393, A 68930), but does not influence the contralateral turning induced by the D2 agonist LY 171555. Studies on the expression of the early gene c-fos as reflected by the immunohistochemical demonstration of the Fos protein, show that administration of scopolamine (5 mg/kg, i.p.) potentiates c-fos expression elicited by SKF 38393 (1.5 mg/kg, s.c.) in the caudate-putamen of the lesioned side. The results indicate that cholinergic transmission is differentially involved in the behavioral expression of D1 versus D2 receptor stimulation in a denervated condition and suggest that blockade of central cholinergic transmission might be useful in improving the antiparkinsonian efficacy of D1 receptor agonists.
Morelli
M
M
Department of Toxicology, University of Cagliari, Italy.
Fenu
S
S
Cozzolino
A
A
Pinna
A
A
Carta
A
A
Di Chiara
G
G
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D018727:Muscarinic Antagonists; D016627:Oxidopamine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D011699:Putamen / Q000187:drug effects / Q000502:physiology; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D015259:Dopamine Agents; D004873:Ergolines; D018727:Muscarinic Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D012601:Scopolamine