[Effect of amantadine on intracranial self-stimulation behavior and cerebral glucose utilization in rats]

Effect of amantadine, an adamantane derivative, was investigated on intracranial self-stimulation behavior and cerebral glucose utilization (CGU) in rats. The experiments were performed on Wistar strain male rats. The low rate responses induced by low current brain stimulation on lateral hypothalamic self-stimulation behavior in a Skinner box were increased by p.o. administration of amantadine at doses of 5 and 10 mg/kg, but were decreased at doses of over 50 mg/kg. Amantadine at doses of 5 and 10 mg/kg, p.o., increased the running speed in run-way performance of animals rewarded with electric stimulation of the medial forebrain bundle in the lateral hypothalamus. On a "conflict" situation induced by combining the hypothalamic self-stimulation with midbrain dorsal central gray stimulation in a Skinner box, amantadine at doses of 5 and 10 mg/kg, p.o. caused an increase of lever pressing in the unpunished period without affecting the punished responses. The CGU measured by [14C] 2-deoxyglucose autoradiography was increased by i.p. administration of 5 mg/kg. In addition, amantadine at a dose of 5 mg/kg, i.p., decreased the high optic density in bilateral habenulae induced by pimozide at 0.75 mg/kg, i.p. These results indicate that amantadine facilitates the intracranial self-stimulation behavior related to a dopaminergic mechanism at low doses, and inhibits the high local CGU of bilateral habenulae induced by pimozide.