Levels of stimulatory G protein are increased in the rat striatum after neonatal lesion of dopamine neurons.
After neonatal lesions of dopamine neurones, an enhanced behavioural responsiveness towards D1 agonists has been described, suggesting a D1 receptor hypersensitivity. In the present study, unilateral striatal dopamine denervation in newborn rats induced a pronounced rotational behaviour following apomorphine injection at the adult age, without any change in the density of D1 binding sites in the denervated striatum. The amount of stimulatory G(olf) alpha subunit was increased by 35% in the lesioned striatum. The large form and the short forms of Gs alpha were also increased by 26% and 9%, respectively. Since in striatal neurones, the coupling of D1 receptor to adenylate cyclase is mostly provided by G(olf) alpha, our results strongly suggest that D1 hypersensitivity described after neonatal dopamine lesions results from an increase in the levels of G(olf) alpha protein.
Penit-Soria
J
J
Laboratoire de Neurochimie-Anatomie, Institute des Neurosciences, URA 1488-CNRS, Université Pierre et Marie Curie, Paris, France.
Durand
C
C
Besson
M J
MJ
Herve
D
D
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D016627:Oxidopamine; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D001058:Apomorphine; D004298:Dopamine