Histamine and spontaneous motor activity: Biphasic changes, receptors involved and participation of the striatal dopamine system

Abstract

The time- and dose-related effects of exogenous histamine on spontaneous motor activity and receptors involved were evaluated in male rats. Intracerebroventricular administration of histamine (5.4 and 54.3 nmol) produced a biphasic effect with initial transitory hypoactivity and later hyperactivity expressed by locomotion frequency in an open-field. The rearing frequencies were only reduced by all doses of histamine used. The histamine-induced hypoactivity was inhibited by the H 3-antagonist thioperamide and was also induced by the H 3-agonist N-α-methylhistamine. The histamine-induced hyperactivity phase was blocked by the H 1-antagonist mepyramine. The H 2-antagonist ranitidine increased locomotion and rearing frequencies. The participation of other neurotransmitters in the persistent hypokinetic effect induced by 135.8 nmol of histamine was determined by HPLC in the striatum and hypothalamus as counter-proof. A decreased DOPAC/DA ratio was observed only in the striatum. In the hypothalamus, low levels of 5HT were detected, probably not correlated with motor activiry. In conclusion, the present results suggest that the exogenous histamine-induced hypoactivity response is probably due to activation of H 3-receptors as heteroreceptors reducing the activity of the striatal dopaminergic system. This effect can partially overlap with the expression of the hyperactivity induced by H 1-receptor activation. The participation of H 2-receptors requires further investigation.