Effects of the histamine (H)3 receptor antagonist ABT-239 on acute and repeated nicotine locomotor responses in rats

The addictive potential of nicotine is linked to psychomotor and cognition-enhancing effects. histamine (h)3 receptor antagonism has similarly received attention for a role in cognition,however,the role of h3 receptors are far less studied for affects on nicotineinduced locomotor responses. in the present study we tested whether the h3 receptor antagonist 4-(2-{2-[(2r)-2methylpyrrolidinyl] ethyl}-benzofuran-5-yl) benzonitrile (abt-239) influenced the psychomotor responses to acute and repeated nicotine,including sensitization and conditioned locomotion. abt-239 (0.3-3 mg/kg) did not alter basal,nicotine-evoked (0.4 mg/kg) locomotor responses,the expression of sensitization,or cue-conditioned locomotion. however,in combination studies rats pretreated with a separate dose of abt-239 (1 mg/kg) prior to nicotine (0.4 mg/kg) for 5 days and then challenged with nicotine (0.4 mg/kg) after a 5-day withdrawal period,showed significantly higher locomotor hyperactivity in comparison with the effect observed in nicotinepretreated and challenged rats. our findings implicate a limited role for h3 receptors in locomotor responses to nicotine. copyright © 2011 by institute of pharmacology polish academy of sciences.