EFFECTS OF THIOPERAMIDE, A HISTAMINE H3 RECEPTOR ANTAGONIST, ON LOCOMOTOR-ACTIVITY AND BRAIN HISTAMINE CONTENT IN MAST CELL-DEFICIENT W/WV MICE

The purpose of this study was to examine the effects of thioperamide, a histamine H-3 antagonist, on the locomotor activity and the brain histamine content in mast-cell-deficient W/W(v) mice. Thioperamide (12.5 and 25 mg/kg) showed significant increase in the locomotor activity of W/W(v) mice, measured by a photobeam system, 1 hr after the intraperitoneal injection. However, more than 75 mg/kg of thioperamide showed not only the reduction of the locomotor activity but also the inhibition of motor coordination measured by the rotarod performance. The increase in the locomotor activity by thioperamide was blocked by i. p. pretreatment with (R)-alpha-methylhistamine, an H-3 agonist, or pyrilamine, an H-1 antagonist, or zolantidine, an H-2 antagonist. The brain histamine content was decreased by thioperamide (12.5-75.0 mg/kg), 1 hr after administration. Thus, the blockade of histamine H-3 receptor by thioperamide showed the activation of locomotor activity of mice, which may be mediated by H-1 and/or H-2 receptors. The present data support the hypothesis that central histaminergic neurons may be involved in the control of state of wakefulness.