title: Histamine H3 receptor agonists decrease hypothalamic histamine levels and increase stereotypical biting in mice challenged with methamphetamine.
abstract: The effects of the histamine H(3) receptor agonists (R)-α-methylhistamine, imetit and immepip on methamphetamine (METH)-induced stereotypical behavior were examined in mice. The administration of METH (10 mg/kg, i.p.) to male ddY mice induced behaviors including persistent locomotion and stereotypical behaviors, which were classified into four categories: stereotypical head-bobbing (1.9%), circling (1.7%), sniffing (14.3%), and biting (82.1%). Pretreatment with (R)-α-methylhistamine (3 and 10 mg/kg, i.p.) significantly decreased stereotypical sniffing, but increased stereotypical biting induced by METH, in a dose-dependent manner. This effect of (R)-α-methylhistamine on behavior was mimicked by imetit or immepip (brain-penetrating selective histamine H(3) receptor agonists; 10 mg/kg, i.p. for each drug). Hypothalamic histamine levels 1 h after METH challenge were significantly increased in mice pretreated with saline. These increases in histamine levels were significantly decreased by pretreatment with histamine H(3) receptor agonists, effects which would appear to underlie the shift from METH-induced stereotypical sniffing to biting.
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan. kitanaka-hyg@umin.net
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitanaka
authors.forename: Nobue
authors.initials: N
authors.lastname: Kitanaka
authors.forename: F Scott
authors.initials: FS
authors.lastname: Hall
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tatsuta
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Morita
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Motohiko
authors.initials: M
authors.lastname: Takemura
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D017442:Histamine Agonists / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D008761:Methylhistamines / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011897:Random Allocation; D013239:Stereotyped Behavior / Q000187:drug effects*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000697:Central Nervous System Stimulants; D017442:Histamine Agonists; D007093:Imidazoles; D008761:Methylhistamines; D010880:Piperidines; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D008694:Methamphetamine; C077430:imetit; C069357:alpha-methylhistamine; D006632:Histamine; D013890:Thiourea