| Autor: |
Rie Tsuchida, Masahiro Kubo, Mariko Kuroda, Yasuhiro Shibasaki, Norihito Shintani, Michikazu Abe, Katalin Köves, Hitoshi Hashimoto, Akemichi Baba |
| Jazyk: |
angličtina |
| Rok vydání: |
2009 |
| Předmět: |
|
| Zdroj: |
Journal of Pharmacological Sciences, Vol 109, Iss 3, Pp 396-402 (2009) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1254/jphs.08297FP |
| Popis: |
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)1A-dependent manner and that amphetamine calmed wild-type mice given the 5-HT1A agonist 8-OH-DPAT. Here, we examined if 5-HT1A–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-HT1A agonist osemozotan. Co-administration of osemozotan with either methamphetamine 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-HT1A antagonist WAY-100635 at a low dose (0.1 mg/kg), suggesting the involvement of a presynaptic 5-HT1A–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. Keywords:: atomoxetine, attention-deficit/hyperactivity disorder (ADHD) medication, locomotor activity, psychostimulant, serotonin 5-HT1A receptor |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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