title: Inhibitory effects of osemozotan, a serotonin 1A-receptor agonist, on methamphetamine-induced c-Fos expression in prefrontal cortical neurons.
abstract: Psychostimulants induce hyperlocomotion in normal subjects, although, they are effective in producing a calming effect in hyperactive subjects. This paradoxical effect has been related to changes in serotonin (5-HT) neurotransmission in hyperactive dopamine transporter-knockout mice. In addition, we observed that hyperlocomotion in mice lacking pituitary adenylate cyclase-activating polypeptide was attenuated by amphetamine dependent on 5-HT(1A) receptor signaling and that amphetamine, when co-administered with a 5-HT(1A) agonist, produced a calming effect in wild-type mice. Here, in an attempt to address how 5-HT(1A) receptor signaling exerts the calming action of psychostimulants, we examined c-Fos expression in several brain regions after administration of methamphetamine and osemozotan, a selective 5-HT(1A) receptor agonist. The number of c-Fos-positive cells was increased in the medial prefrontal cortex, striatum and nucleus accumbens in methamphetamine (3 mg/kg body weight)-injected mice. Osemozotan (1 mg/kg) significantly reduced the methamphetamine-induced c-Fos expression in the medial prefrontal cortex and striatum, but not in the nucleus accumbens. This osemozotan action was completely blocked by the 5-HT(1A) receptor antagonist WAY-100635 (1 mg/kg). As the prefrontal cortex is considered to be involved in the beneficial actions of psychostimulant medications for attention-deficit/hyperactivity disorder, the present result showing 5-HT(1A)-mediated inhibition of corticostriatal activity may partly be related to this psychostimulant action.
authors.affiliation: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Tsuchida
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kubo
authors.forename: Norihito
authors.initials: N
authors.lastname: Shintani
authors.forename: Michikazu
authors.initials: M
authors.lastname: Abe
authors.forename: Katalin
authors.initials: K
authors.lastname: Köves
authors.forename: Kazuki
authors.initials: K
authors.lastname: Uetsuki
authors.forename: Mariko
authors.initials: M
authors.lastname: Kuroda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Akemichi
authors.initials: A
authors.lastname: Baba