THIOPERAMIDE, THE SELECTIVE HISTAMINE-H-3 RECEPTOR ANTAGONIST, ATTENUATES STIMULANT-INDUCED LOCOMOTOR-ACTIVITY IN THE MOUSE

The effects of the selective histamine H-3 receptor agonist (R)-alpha-methylhistamine and antagonist thioperamide on stimulant-induced locomotor activity in the mouse were examined. Amphetamine (1 mg.kg(-1) s.c.), apomorphine (2 mg.kg(-1) s.c.) or cocaine (5 mg.kg(-1) s.c.) increased locomotor activity. Neither thioperamide (10 mg.kg(-1) i.p.) nor (R)-alpha-methylhistamine (20 mg.kg(-1) i.p.) affected spontaneous locomotor activity in their own right. (R)-alpha-Methylhistamine (0.3, 3 or 20 mg.kg(-1) i.p.) also had no effect on amphetamine (1 mg.kg(-1) s.c.)-induced locomotor activity. In contrast, thioperamide (0.2-10 mg.kg(-1) i.p. or 0.3-20 mu g i.c.v.) inhibited, in a dose-dependent manner, the hyperactivity response induced by amphetamine (1 mg.kg(-1) s.c.). (R)-alpha-Methylhistamine (20 mg.kg(-1) i.p.) completely reversed the inhibitory response to thioperamide (2 mg.kg(-1) i.p.). Thioperamide (2 or 10 mg.kg(-1) i.p.) also inhibited apomorphine (2 mg.kg(-1) s.c.)- and, to a lesser extent, cocaine (5 mg.kg(-1) s.c.)-induced hyperactivity. We therefore conclude that antagonism of the central histamine H-3 receptor inhibits, to a varying degree, the effects of locomotor stimulants.