title: Lithium attenuates methamphetamine-induced hyperlocomotion and behavioral sensitization via modulation of prefrontal monoamine release.
abstract: Lithium attenuates psychostimulant-induced hyperactivity and behavioral sensitization, but the exact mechanisms are not known. Previous studies show that lithium has neuromodulatory effects on monoamine systems. The present study was aimed to clarify whether prefrontal monoaminergic neurotransmission is involved in the effect of lithium on methamphetamine (METH)-induced behaviors in mice. Lithium attenuated METH-induced hyperactivity and METH-induced increase in extracellular dopamine (DA), but not serotonin (5-HT), levels in the prefrontal cortex. Chronic METH caused behavioral sensitization and enhancement of METH-induced increase in prefrontal 5-HT release (neurochemical sensitization). Co-administration of lithium with METH attenuated behavioral sensitization and neurochemical sensitization. Chronic METH also reduced the 5-HT(1A) receptor agonist osemozotan-induced decrease in prefrontal 5-HT release (desensitization of presynaptic 5-HT(1A) autoreceptor), and this effect was reversed by co-administration of lithium. These results suggest that lithium attenuates acute METH-induced hyperactivity and chronic METH-induced behavioral sensitization via modulation of prefrontal release of DA and 5-HT, respectively. The present study also suggests that a 5-HT(1A) receptor-mediated mechanism is involved in the effect of lithium on chronic METH-induced behavioral sensitization.
authors: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Yukio
authors: Y
authors: Ago
authors: Tatsunori
authors: T
authors: Tanaka
authors: Yuki
authors: Y
authors: Kita
authors: Hokuto
authors: H
authors: Tokumoto
authors: Kazuhiro
authors: K
authors: Takuma
authors: Toshio
authors: T
authors: Matsuda
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: D018765:Dopamine Uptake Inhibitors; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D008694:Methamphetamine; D018021:Lithium Chloride; D004298:Dopamine