RESUMO
RATIONALE AND OBJECTIVES: 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. RESULTS: 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. CONCLUSIONS: These data suggest that dopaminergic systems in the NAc may play important roles in p-OHA-induced locomotor activity in rodents.
Assuntos
Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Dopamina/metabolismo , Atividade Motora/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , p-Hidroxianfetamina/administração & dosagem , Animais , Ditiocarb/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Dopamina beta-Hidroxilase/antagonistas & inibidores , Dopamina beta-Hidroxilase/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Fluoxetina/farmacologia , Injeções Intraventriculares , Masculino , Camundongos , Microinjeções , Vias Neurais/metabolismo , Nomifensina/farmacologia , Núcleo Accumbens/metabolismo , Ratos , Ratos Wistar , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Fatores de TempoRESUMO
It is well known that head-twitch response (HTR) in mice represents hallucinations, since administration of lysergic acid diethylamide (LSD) produces hallucinations in humans, and the HTR in mice is induced by administration of LSD as a hallucinogen. The HTR is produced by excitation of 5-hydroxytryptamine (5-HT)2A receptors. In this paper, we review the mechanisms of HTR induced by various drugs such as 5-HT precursor, 5-HT receptor agonist, 5-HT releaser, hallucinogenic compounds, benzodiazepins and cannabinoid. The response induced by HTR-inducers is significantly enhanced by combined treatment with a non-selective form of monoamine oxidase (MAO) inhibitor. Thus, the relationship between MAO activity and HTR caused by these drugs (especially, alpha-methylated analogous compounds which 5-fluoro-alpha-methyltryptamine, 6-fluoro-alpha-methyltryptamine and p-hydroxyamphetamine) is presented in detail.
