Effects of Rubidium on Behavioral Responses to Methamphetamine and Tetrabenazine

Abstract

Abstract-Different groups of mice were injected subcutaneoLisly every other day with rubidium chloride at three doses (0.41(50), 1.23(150) and 3.69(450) meq,'kg (mg/kg)) or with saline as a control for a period of 2-3 weeks. Rubidium administered acutely did not affect spontaneous locomotor activities, while it tended to increase the activities when administered repeatedly though the increase was not statistically significant. The methamphetamine-induced hyperlocomotor activities were potentiated in the rubidium groups as compared with those in the saline group, this effect of rubidium being in creased with prolongation of repeated administrations. Monotonic decreases in ambu lation after tetrabenazine were not significantly affected in the rubidium-treated animals though the decreases were sometimes preceded by slight increases and recovery from the decrement tended to be more rapid. After tetrabenazine in the rubidium-treated groups, incidences of catalepsy were increased and jumping behavior and Straub tail responses occurred in a few cases. The results suggest that rubidium potentiates the excitatory action of methamphetamine on spontaneous locomotor activities, as con trasted with inhibitory influence of lithium.Rubidium and lithium, alkaline metals, have been proposed to have valuable therapeutic and prophylactic effects in manic-depressive psychosis; rubidium is principally effective in depressive states (1, 2) while lithium is effective mainly for manic states. In studies on ani mals, the behavioral activation caused by morphine is potentiated by rubidium in mice whereas it is antagonized by lithium (3). Thus rubidium and lithium presumably have opposite effects in all species.Many studies have also been done on the neurochemical mechanisms underlying the affective disorders. The catecholamine hypothesis of affective disorders is that some, if not all, depressions are associated with an absolute or relative decrease in catecholamines, available at central adrenergic receptors sites, while elation, conversely, may be associated with an excess of such amines (4, 5). Associated with this hypothesis has been the proposal by one of the present authors (T.F.) that lithium modifies behavioral responses to me thamphetamine and tetrabenazine and that these drugs act on the metabolism of endogenous brain catecholamines, inhibiting in particular the methamphetamine-induced excitation (6).The present investigation was an attempt to study the effects of rubidium on behavioral responses induced by methamphetamine and tetrabenazine. MATERIALS AND METHODSHealthy ddY male albino mice obtained from the Kuroda Animal Laboratory (Kuma