An antihyperkinetic action by the serotonin la-receptor agonist osemozotan co-administered with psychostimulants or the non-stimulant atomoxetine in mice

Rie Tsuchida, Masahiro Kubo, Mariko Kuroda, Yasuhiro Shibasaki, Norihito Shintani, Michikazu Abe, Katalin Koves, Hitoshi Hashimoto, Akemichi Baba

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7 Citations (Scopus)

Abstract

It has been demonstrated that treatment of hyperactive mice with psychostimulants produced a calming effect depending on serotonergic neurotransmission. Our previous study also showed that hyperactivity in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) was ameliorated by amphetamine in a serotonin (5-HT)iA-dependent manner and that amphetamine calmed wild-type mice given the 5-HTiA agonist 8-OH-DPAT. Here, we examined if 5-HTiA-mediated pathways can be a determinant of the action of other psychostimulants as well as the non-stimulant atomoxetine by examining locomotor activity in mice co-administered with the 5-HTiA agonist osemozotan. Co-administration of osemozotan with either methamphet- amine or amphetamine was not only antihyperkinetic, but also decreased locomotion to below basal levels. In contrast, osemozotan just nullified methylphenidate-induced hyperactivity. The non-stimulant atomoxetine did not induce hyperactivity, but co-administration of atomoxetine with osemozotan produced a calming effect. The adjunctive effect of osemozotan added to the psychostimulants was blocked by the 5-HTia antagonist WAY-100635 at a low dose (0.1 mg /kg), suggesting the involvement of a presynaptic 5-HTiA-mediated mechanism. However, WAY-100635 (up to 1 mg/kg) did not block the effect of atomoxetine plus osemozotan. The present results may provide insights into the therapeutic mechanisms of the psychostimulants and atomoxetine for hyperkinetic disorders.

Original languageEnglish
Pages (from-to)396-402
Number of pages7
JournalJournal of Pharmacological Sciences
Volume109
Issue number3
DOIs
Publication statusPublished - Jun 22 2009

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Keywords

  • Atomoxetine
  • Attention-deficit /hyperactivity disorder (ADHD) medication
  • Locomotor activity
  • Psychostimulant
  • Serotonin 5-HT1A receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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