title: Increased methamphetamine-induced locomotor activity and behavioral sensitization in histamine-deficient mice.
abstract: We have recently suggested that the brain histamine has an inhibitory role on the behavioral effects of methamphetamine by pharmacological studies. In this study, we used the histidine decarboxylase gene knockout mice and measured the spontaneous locomotor activity, the changes of locomotion by single and repeated administrations of methamphetamine, and the contents of brain monoamines and amino acids at 1 h after a single administration of methamphetamine. In the histidine decarboxylase gene knockout mice, spontaneous locomotor activity during the dark period was significantly lower than in the wild-type mice. Interestingly, methamphetamine-induced locomotor hyperactivity and behavioral sensitization were facilitated more in the histidine decarboxylase gene knockout mice. In the neurochemical study, noradrenaline and O-phosphoserine were decreased in the midbrain of the saline-treated histidine decarboxylase gene knockout mice. On the other hand, single administration of methamphetamine decreased GABA content of the midbrain of the wild-type mice, but did not alter that of histidine decarboxylase gene knockout mice. These results suggest that the histamine neuron system plays a role as an awakening amine in concert with the noradrenaline neuron system, whereas it has an inhibitory role on the behavioral effects of methamphetamine through the interaction with the GABAergic neuron system.
authors.affiliation: Department of Psychiatry, Tohoku University, Graduate School of Medicine, Sendai, Japan. kkubotaya@mail.cc.tohoku.ac.jp
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kubota
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ito
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sakurai
authors.forename: Eiko
authors.initials: E
authors.lastname: Sakurai
authors.forename: Takehiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000032:analysis; D006632:Histamine / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000172:deficiency / Q000235:genetics; D006719:Homovanillic Acid / Q000032:analysis; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000032:analysis; D010768:Phosphoserine / Q000032:analysis; D017440:Photoperiod; D012701:Serotonin / Q000032:analysis; D005680:gamma-Aminobutyric Acid / Q000032:analysis
chemical_list: D000596:Amino Acids; D015102:3,4-Dihydroxyphenylacetic Acid; D010768:Phosphoserine; D012701:Serotonin; D008694:Methamphetamine; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D006640:Histidine Decarboxylase; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid