Psychopharmacology 2010-02-01

Central administration of p-hydroxyamphetamine produces a behavioral stimulant effect in rodents: evidence for the involvement of dopaminergic systems.

Hiroshi Onogi, Masato Hozumi, Osamu Nakagawasai, Yuichiro Arai, Seiichiro Ishigaki, Atsushi Sato, Seiichi Furuta, Fukie Niijima, Koichi Tan-No, Takeshi Tadano

Index: Psychopharmacology 208(2) , 323-31, (2010)

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Abstract

It is well-known that amphetamine induces increased locomotor activity in rodents. We previously found that intracerebroventricular (i.c.v.) administration of p-hydroxyamphetamine (p-OHA), an amphetamine metabolite, increases synaptic dopamine (DA) levels in the striatum. In the present study, we investigated the effect of p-OHA on locomotor activity in rodents.In mice, i.c.v. administration of p-OHA significantly increased locomotor activity in a dose-dependent manner. p-Hydroxynorephedrine, another amphetamine metabolite, did not increase locomotor activity. This effect of p-OHA was inhibited by pretreatment with nomifensine, a dopamine-uptake inhibitor, but not by fluoxetine, a serotonin-uptake inhibitor, or diethyldithiocarbamate, a dopamine-beta-hydroxylase inhibitor. Furthermore, we tested the effects of microinjections of p-OHA into the rat nucleus accumbens (NAc) on locomotor activity. Local infusion of p-OHA into the NAc significantly increased locomotor activity. As in mice, the increased locomotor activity induced by p-OHA microinjection into the NAc in rats was inhibited by nomifensine.These data suggest that dopaminergic systems in the NAc may play important roles in p-OHA-induced locomotor activity in rodents.