Pharmacological basis for N- n-propylnoramorphine induced stereotypic cage climbing and behavioral arousal in mice

Abstract

Apmorphine (APO) and its N-propyl homologue (N- n-propylnorapomorphine; NPA) are approximately equipotent in inducing stereotypic cage climbing and behavioral arousal. The time courses for the two behavioral responses of both aporphines are also quite similar. These results suggested that aporphine-induced stereotypic cage-climbing and behavioral arousal, if specific for dopamine receptor stimulation, could provide useful in vivo models for predicting dose- and time-response effects of potential antiparkinsonian agents. In the present experiments, six neurotransmitter receptor blockers (alropine, phentolamine, sotalol, cyproheptadine, naloxone, and haloperidol or spiroperidol) were compared in mice for their ability to alter cage climbing and behavioral arousal induced by NPA. Results indicated that pretreatment with the dopamine blockers haloperidol and spiroperidol, significantly antagonized both responses to NPA and shifted the cage climb dose response curve to the right 15-fold. In contrast, the muscarinic cholinergic (atropine), alpha-noradrenergic (phentolamine), beta-noradrenergic (sotalol), serotonergic (cyproheptadine), and opiate (naloxone) receptor blockers uniformly did not attenuate activity due to NPA. These results suggest that cage-climbing and arousal induced by aporphines is mediated via dopamine receptor stimulation and that these responses provide useful in vivo models for accurate evaluation of certain classes of dopamine agonists with clinical utility.