1P411 Brain-penetrating H1-antagonists enhanced the methamphetalnine-induced behavioral sensitization

• Published in: Journal of Pharmacological Sciences Vol. 91; no. suppl.1; p. 171
• Main Authors: Tomohiro Okuda, Kentaro Iwabuchi, Zhong Chen, Masatoshi Endo, Eiko Sakurai, Kazuhiko Yanai
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 2003
• ISSN: 1347-8613

Methamphetamine is known to cause increased locomotor activity, stereotyped behaviors and disruption of prepulse inhibition (PPI). Histaminergic neurons are proposed to have an inhibitory effect on the behavioral sensitization activated by the dopaminergic neuron system. We investigated the effects of H1 antagonists on methamphetamine-induced behavioral sensitization. Male S-D rats were used to develop the methamphetamine (3mg/kg i,p.)-induced sensitization. d-chlorpheniramine (1, 2. 5, 7.5 mg/kg i.p.), l-chlorpheniramine (7.5 mg/kg i,p.), and ebastine (10 mg/kg i,p.) were simultaneously administered. Locomotor activities for 360 min and acoustic startle responses at 30 and 180 min were measured after the drugs administration. Combination of methamphetamine and d- and l-chlorpheniramine prolonged the duration of methamphetamine-induced increased locomotor activity and showed the enhanced disruption of PPI at 180 min after drug administration when compared to methamphetamine alone. The effects of d-chlorpheniramine were greater than those of the l-isomer. Ebastine, a second generation H1 antagonist, had no effects on the methamphetamine-induced behavioral sensitization. These results suggested that the brain-penetrating antihistamines could enhance the methamphetamine-induced behavioral sensitization probably due to dual mechanisms of the inhibition of dopamine uptake and H1 antagonism.