An antihyperkinetic action by the serotonin 1A-receptor agonist osemozotan co-administered with psychostimulants or the non-stimulant atomoxetine in mice
Tsuchida, R; Kubo, M; Kuroda, M; Shibasaki, Y; Shintani, N; Abe, M; Köves, K; Hashimoto, H; Baba, A
| HERO ID | 3539170 |
|---|---|
| In Press | No |
| Year | 2009 |
| Title | An antihyperkinetic action by the serotonin 1A-receptor agonist osemozotan co-administered with psychostimulants or the non-stimulant atomoxetine in mice |
| Authors | Tsuchida, R; Kubo, M; Kuroda, M; Shibasaki, Y; Shintani, N; Abe, M; Köves, K; Hashimoto, H; Baba, A |
| Journal | Journal of Pharmacological Sciences |
| Volume | 109 |
| Issue | 3 |
| Page Numbers | 396-402 |
| 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)(1A)-dependent manner and that amphetamine calmed wild-type mice given the 5-HT(1A) agonist 8-OH-DPAT. Here, we examined if 5-HT(1A)-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-HT(1A) 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-HT(1A) antagonist WAY-100635 at a low dose (0.1 mg/kg), suggesting the involvement of a presynaptic 5-HT(1A)-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. |
| Pmid | 19270432 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |