Neuropsychotoxicity of Abused Drugs:Effects of Serotonin Receptor Ligands on Methamphetamine- and Cocaine-Induced Behavioral Sensitization in Mice

Journal of Pharmacological Sciences

Akemichi Baba²  Yukio Ago¹  Shigeo Nakamura¹  Toshio Matsuda¹ 

[1] Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan;Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan

关键词: drugs of abuse;    behavioral sensitization;    methamphetamine;    cocaine;    serotonin (5-HT)-receptor ligand;   

DOI  :  10.1254/jphs.FM0070121

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(47)Cited-By(18)Repeated administration of psychostimulants elicits a progressive enhancement of locomotor activity known as behavioral sensitization. Central dopamine (DA) neurons play key roles as the neural substrates mediating behavioral sensitization, but the role of the serotonin (5-HT) system in the sensitization is not fully elucidated. We have recently demonstrated that osemozotan, a specific 5-HT1A–receptor agonist, and ritanserin, a 5-HT2–receptor antagonist, inhibited the expression and development of both methamphetamine- and cocaine-induced behavioral sensitization in mice and that these drugs attenuated the maintenance of behavioral sensitization of methamphetamine, but not that of cocaine. We also found that azasetron, a 5-HT3–receptor antagonist, inhibited the expression and development of the sensitization induced by methamphetamine and cocaine, respectively. Neurochemical studies using a microdialysis technique showed that repeated methamphetamine enhanced the methamphetamine-induced increase in 5-HT release in the prefrontal cortex. The sensitization of 5-HT release in methamphetamine-treated mice was attenuated by osemozotan and ritanserin. These findings suggest that the 5-HT system plays an important role in methamphetamine- and cocaine-induced behavioral sensitization in mice and imply that 5-HT1A–receptor agonists and 5-HT2–receptor antagonists may have a potential therapeutic value for the treatment of methamphetamine abuse or psychosis.

【 授权许可】

Unknown