title: Role of Prefrontal Serotonergic and Dopaminergic Systems in Encounter-Induced Hyperactivity in Methamphetamine-Sensitized Mice.
abstract: Isolation-reared mice show social encounter-induced hyperactivity with activation of prefrontal serotonergic and dopaminergic systems, but it is not known whether this stress response is observed in other pathological conditions. Here we examined whether the social encounter stimulation induces abnormal behavior during withdrawal in chronic methamphetamine-treated mice.
  
  
  
  To induce methamphetamine-induced behavioral sensitization, male mice were injected with methamphetamine (1 mg/kg) once daily for 7 days.
  
  
  
  The encounter with an intruder elicited hyperactivity 24 h after the last injection of methamphetamine in methamphetamine-sensitized mice. This response was observed even as long as 2 weeks after withdrawal of methamphetamine. The encounter increased c-Fos expression in the prefrontal cortex, dorsal raphe nucleus and ventral tegmental area in methamphetamine-sensitized mice, while it did not in control mice. Furthermore, the encounter increased extracellular serotonin (5-HT) and dopamine, but not noradrenaline, levels in the prefrontal cortex in methamphetamine-sensitized mice. Local injection of 5,7-dihydroxytryptamine and 6-hydroxydopamine into the prefrontal cortex attenuated encounter-induced hyperactivity in methamphetamine-sensitized mice and it markedly decreased prefrontal 5-HT and dopamine levels, respectively. Pharmacological analysis showed that the encounter-induced hyperactivity is mediated by dopamine D1 receptors and 5-HT2A receptors and attenuated by anxiolytics and antidepressants such as diazepam, osemozotan and selective 5-HT reuptake inhibitors. The effect of paroxetine was blocked by the 5-HT3 receptor antagonist azasetron.
  
  
  
  The present study shows that psychological stress elicits hyperactivity with activation of prefrontal 5-HT and dopamine systems in methamphetamine-dependent mice and suggests that the abnormal behavior is associated with anxiety and depression.
authors.affiliation: Laboratory of Molecular Neuropharmacology, Osaka University, Osaka, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Laboratory of Molecular Neuropharmacology, Osaka University, Osaka, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.affiliation: Laboratory of Molecular Neuropharmacology, Osaka University, Osaka, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Umehara
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Emina
authors.initials: E
authors.lastname: Imoto
authors.affiliation: Department of Pharmacology, Graduate School of Dentistry, Osaka University, Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hasebe
authors.affiliation: Laboratory of Molecular Neuropharmacology, Osaka University, Osaka, Japan.|United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, and University of Fukui, Osaka, Japan.|Division of Bioscience, Institute for Datability Science, Osaka University, Osaka, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Department of Pharmacology, Graduate School of Dentistry, Osaka University, Osaka, Japan.|United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, and University of Fukui, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003891:Desipramine / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006948:Hyperkinesis / Q000139:chemically induced* / Q000188:drug therapy; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D017551:Microdialysis; D016627:Oxidopamine / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D012919:Social Behavior; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D008694:Methamphetamine; D016627:Oxidopamine; D003891:Desipramine; D004298:Dopamine
keywords: dopamine; encounter; hyperactivity; methamphetamine; serotonin