title: Effects of the histamine H3 receptor antagonist ABT-239 on acute and repeated nicotine locomotor responses in rats.
abstract: 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 H(3) receptors are far less studied for affects on nicotine-induced locomotor responses. In the present study we tested whether the H(3) receptor antagonist 4-(2-{2-[(2R)-2 methylpyrrolidinyl] 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 nicotine-pretreated and challenged rats. Our findings implicate a limited role for H(3) receptors in locomotor responses to nicotine.
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Miszkiel
authors.forename: Marta
authors.initials: M
authors.lastname: Kruk
authors.forename: Andrew C
authors.initials: AC
authors.lastname: McCreary
authors.forename: Edmund
authors.initials: E
authors.lastname: Przegaliński
authors.forename: Grażyna
authors.initials: G
authors.lastname: Biała
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D054828:Histamine H3 Antagonists / Q000633:toxicity*; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage*; D011759:Pyrrolidines / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000378:metabolism*
chemical_list: D001572:Benzofurans; D054828:Histamine H3 Antagonists; D011759:Pyrrolidines; D018100:Receptors, Histamine H3; D009538:Nicotine; C496397:benzonitrile, 4-(2-(2-((2r)-2-methyl-1-pyrrolidinyl)ethyl)-5-benzofuranyl)-