Use of the Intracerebral Injection Technique to Elucidate Mechanisms of Apomorphine Climbing and Its Antagonism in the Mouse

Climbing behavior induced by peripherally administered apomorphine in the mouse was reduced by 0.25-10 microgram bilateral intra-accumbens fluphenazine, (+/-) and (-) sulpiride and by serotonin, but not by (+)sulpiride, dl-propranolol, phentolamine, atropine or methysergide. A specific antagonism of climbing could not be shown when fluphenazine was injected into the striatum, hypothalamus, thalamus, reticular formation, frontal cortex or cerebellum, but was apparent when a large dose of fluphenazine was placed below (but not above) the accumbens nucleus. 6-Hydroxydopamine denervation of the nucleus accumbens did not alter the climbing antagonism afforded by fluphenazine, although sulpiride was three-fold more effective following denervation. The data indicates an accumbens involvement in the climbing phenomenon, that sulpiride more effectively antagonises climbing after accumbens denervation and that the presumed dopamine agonist-antagonist interaction in the accumbens, which controls climbing, may also involve serotonergic function. The studies emphasise the value of the intra-cerebral injection technique to an analysis of drug action in the mouse.