Attenuation by the 5-HT1A receptor agonist osemozotan of the behavioral effects of single and repeated methamphetamine in mice.
This study examined the effects of the selective 5-HT1A receptor agonist osemozotan on repeated methamphetamine (METH)-induced behavioral sensitization and single METH-induced locomotor stimulant effect in mice, and then the neurochemical mechanisms using in vivo microdialysis. Repeated administration of METH for 7 days enhanced METH challenge-induced locomotor activity, and this sensitization was observed even after its withdrawal for 7-14 days. Administration of osemozotan to METH-sensitized mice inhibited the maintenance of behavioral sensitization. This effect was blocked by a low dose of WAY100635, a selective 5-HT1A receptor antagonist. A METH challenge increased the extracellular levels of dopamine (DA), 5-HT, and noradrenaline in the prefrontal cortex, but only the increase in 5-HT release was enhanced by repeated METH administration. This augmented response of 5-HT release was attenuated by osemozotan in a WAY100635-sensitive way. A single administration of osemozotan to drug naïve mice inhibited METH-induced locomotor stimulant effect and reduced METH-induced increase in prefrontal 5-HT, but not DA, release. These results suggest that prefrontal 5-HT release is involved at least partly in the effects of osemozotan on single and repeated METH-induced behavioral effects in mice, and imply that the 5-HT1A receptors may have a potential therapeutic value in the remission of schizophrenia.
Ago
Yukio
Y
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Nakamura
Shigeo
S
Uda
Misato
M
Kajii
Yasushi
Y
Abe
Michikazu
M
Baba
Akemichi
A
Matsuda
Toshio
T
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004146:Dioxanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004563:Electrochemistry / Q000379:methods; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D004146:Dioxanes; D004149:Dioxoles; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D008694:Methamphetamine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C096294:osemozotan