title: Modulation of the discriminative stimulus effects of cocaine and methamphetamine by the histaminergic system.
abstract: The role of the histaminergic system in the discriminative stimulus effects of cocaine and methamphetamine was examined in rats trained to discriminate between saline and cocaine (10 mg/kg) or methamphetamine (1.0 mg/kg). L-histidine (400 mg/kg), a precursor of histamine, significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine. Previous studies have revealed the existence of several histamine receptor types, H1-, H2-, and H3-receptors. These enhancing effects of L-histidine on the discriminative stimulus effects of cocaine and methamphetamine were attenuated by 5.0 mg/kg of pyrilamine (an H1-receptor antagonist), but not by 1.0 mg/kg of zolantidine (an H2-receptor antagonist), suggesting that these enhancing effects of L-histidine were mediated through the activation of H1-receptors. Thioperamide (7.5 mg/kg), an H3-receptor antagonist, also significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine. However, neither pyrilamine nor zolantidine affected the enhancing effects of thioperamide, unlike the results attained with L-histidine. Therefore our findings suggest that the histaminergic system may modify the discriminative stimulus effects of cocaine and methamphetamine mediated through H1- and H3-receptors.
authors.affiliation: Department of Toxicology, School of Pharmacy, Hoshi University, Shinagawa-ku, Tokyo, 142-8501 Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Mori
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Kenji
authors.initials: K
authors.lastname: Onodera
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004357:Drug Synergism; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011969:Receptors, Histamine H1 / Q000502:physiology; D018100:Receptors, Histamine H3 / Q000502:physiology
chemical_list: D000697:Central Nervous System Stimulants; D006633:Histamine Antagonists; D010880:Piperidines; D011969:Receptors, Histamine H1; D018100:Receptors, Histamine H3; D008694:Methamphetamine; D006639:Histidine; D006632:Histamine; D003042:Cocaine; C052075:thioperamide