[Effects of an ergot derivative, lisuride, on the central dopaminergic system -- studies of behavioral pharmacology]

The central dopaminergic (DA) activity of lisuride hydrogen maleate (lisuride) was investigated from the view point of behavioral pharmacology in rats and mice. Lisuride exhibited a biphasic action on locomotor activity in mice and rats; with low doses lisuride caused hypomotility, whereas higher doses produced locomotor stimulation. The hypomotility induced by lisuride (0.00625 mg/kg, s.c.) was antagonized by a low dose of sulpiride (10 mg/kg, i.p.) in rats, and the lisuride (0.05 mg/kg)-induced hyperactivity was inhibited with haloperidol (0.1 mg/kg, i.p.). The stimulatory effect of lisuride on locomotion was not affected by the combined pretreatment with reserpine and alpha-methyl-p-tyrosine. The hyperactivity of mice induced by methamphetamine was inhibited by pretreatment with lisuride. In the rat lesioned unilaterally in the nigro striatal pathway by a local injection of 6-hydroxydopamine, a low dose of lisuride induced rotational behavior contralateral to the side of the lesion, and the rotational behavior was inhibited by pretreatment with haloperidol. These results indicate that lisuride at low doses effectively stimulates pre-synaptic DA receptors and the post-synaptic DA receptor under supersensitization in the mesolymbic and nigro striatal systems.