Behavioral effects of lithium on presynaptic sites of catecholaminergic neurons in the mouse.

The effect of lithium on locomotor activity in mice was studied and an attempt was made to elucidate the neuronal mechanisms involved. Lithium chloride (200 mg/kg, i.p.) administered acutely or daily for 7 days did not affect locomotor activity. A single injection of apomorphine at a low dose of 0.25 mg/kg (i.p.) markedly decreased locomotor activity but repeated injection of the drug produced hyperlocomotion accompanied by sniffing. Methamphetamine (1 mg/kg, i.p.), haloperidol (0.02 mg/kg, i.p.), thyrotropin releasing hormone (5 mg/kg, i.p.) or apomorphine (1 mg/kg, i.p.) exerted a biphasic action in locomotor activity, i.e. an initial increase and subsequent decrease. This initial hyperlocomotion induced by these drugs, except for apomorphine, was inhibited by lithium (200 mg/kg, i.p. X 1) or a low dose of apomorphine (0.25 mg/kg, i.p. X 1). The subsequent hypolocomotion was also attenuated by lithium, but not by apomorphine. Imipramine (10 mg/kg, i.p.) increased the hyperlocomotion induced by methamphetamine. The inhibitory effect of tetrabenazine (5 mg/kg, i.p.) on locomotor activity was attenuated after repeated treatment with lithium (200 mg/kg, i.p. X 7) or imipramine (10 mg/kg, i.p. X 7). The results suggest that lithium may inhibit dopaminergic neuron activities, probably not through an activation of presynaptic dopamine autoreceptors.