Adenosine 3',5'-cyclic monophosphate as a possible mediator of rotational behaviour induced by dopaminergic receptor stimulation in rats lesioned unilaterally in the substantia nigra.
A possible involvement of c-AMP in the rotational behaviour induced by a stimulation of dopamine receptors in corpus striatum of rats was investigated. Rats were lesioned unilaterally in the substantia nigra with 6-hydroxydopamine. Intraventricular injection of dopamine, norepinephrine and apomorphine induced rotational behaviour towards the intact side as did dibutyryl c-AMP (dB-c-AMP). Dopamine, norepinephrine and apomorphine could activate adenylate cyclase in homogenates of caudate nucleus. The activation by dopamine was blocked by haloperidol. I.p. injected apomorphine increased c-AMP content bilaterally in caudate nucleus and caused turning towards the intact side; theophylline potentiated and haloperidol blocked the effect. In non-lesioned rats, dopamine and norepinephrine, when injected unilaterally into the caudate nucleus, elicited truning twoards the non-injected side if the rats were pretreated with reserpine and tranylcypromine. c-AMP and dB-c-AMP given similarly to rats pretreated with theophylline also produced turning towards the non-injected side regardless the pretreatment with reserpine and tranylcypromine. All these results emphasize the possibility that c-AMP acts as a second messenger in the central dopaminergic pathway in rats. The supersensitivity of the dopaminergic system which developed after denervation is also discussed.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D002421:Caudate Nucleus / Q000032:analysis / Q000201:enzymology; D000242:Cyclic AMP / Q000032:analysis / Q000502:physiology*; D003714:Denervation; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013378:Substantia Nigra / Q000032:analysis / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology
D011954:Receptors, Dopamine; D013806:Theophylline; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006220:Haloperidol; D001058:Apomorphine