Role of histamine H₁ receptor in caffeine induced locomotor sensitization

The present study elucidated the role of histamine H₁ receptor in the caffeine induced locomotor sensitization. Intermittent administration of caffeine (15 mg/kg, i.p.) on alternate days (induction phase) i.e. 1^st, 3^rd, 5^th, 7^th, 9^th, 11^th and 13^th resulted in the development of locomotor sensitization. In addition, challenge with sub-stimulant dose of caffeine (10 mg/kg, i.p.) directly on 17^th day to induction group animals resulted in expression to locomotor sensitization to caffeine. I.c.v. injection of histaminergic agents concomitantly with caffeine during induction phase i.e. histamine H₁ receptor agonist, FMPH (6.5 μg/mouse) significantly potentiated while H₁ receptor antagonist, cetirizine (0.1 μg/mouse) attenuated the locomotor sensitization induced by caffeine (15 mg/kg, i.p.). In addition, challenge with caffeine (10 mg/kg, i.p.) on the expression day (17^th) to the induction group mice on FMPH + caffeine treatment showed enhanced, while those on cetirizine + caffeine treatment exhibited lesser expression to locomotor sensitization. Therefore, a possible contributory role of the central histaminergic system via H₁ receptor stimulation or up-regulation in the caffeine-induced locomotor sensitizing effect is proposed.