Effects of Dopamine- and Serotonin-Related Compounds on Methamphetamine-Induced Self-Injurious Behavior in Mice

Journal of Pharmacological Sciences

Toshiko Sawaguchi¹  Shinobu Ito¹  Taizo Kita²  Tomohisa Mori¹ 

[1] Department of Legal Medicine, Tokyo Women’s Medical University;Section of Addictive Drugs Research, Division of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry

关键词: methamphetamine;    self-injurious behavior;    dopamine;    serotonin;   

DOI  :  10.1254/jphs.FPJ04040X

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(41)Cited-By(15)Methamphetamine induces hyperlocomotion, and high doses of methamphetamine induce self-injurious behavior (SIB) in rodents. It is well known that the monoaminergic system is involved in methamphetamine-induced behavior. However, the effects of dopamine- and serotonin (5-HT)-related compounds on high-dose methamphetamine-induced behavior have not been sufficiently clarified. Therefore, the present study was designed to investigate the effects of dopamine receptor antagonists and indirect 5-HT receptor agonists on high-dose methamphetamine-induced behavior in mice. Methamphetamine (20 mg/kg) initially increased locomotor activity. As the dosage increased, continuous SIB accompanied by a reduction in locomotor activity was observed. The hyperlocomotion and SIB induced by 20 mg/kg of methamphetamine was abolished by high doses of SCH23390 and haloperidol, indicating that the hyperlocomotion and SIB induced by high doses of methamphetamine are mediated by the activation of D1- and D2-receptors. Furthermore, haloperidol (0.1 mg/kg) potently increased locomotor activity in combination with 20 mg/kg methamphetamine. These results suggest that excess dopaminergic activation, especially activation of dopamine D2-receptors, may be involved in the decrease in locomotor activity induced by a high dose of methamphetamine. On the other hand, indirect 5-HT receptor agonists attenuated methamphetamine-induced SIB, suggesting that the stimulation of 5-HT receptors plays an important role in high-dose methamphetamine-induced SIB in mice.

【 授权许可】

Unknown