Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
Neuropsychotoxicity of Abused Drugs: Effects of Serotonin Receptor Ligands on Methamphetamine- and Cocaine-Induced Behavioral Sensitization in Mice
Yukio AgoShigeo NakamuraAkemichi BabaToshio Matsuda
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JOURNALS FREE ACCESS Advance online publication

Article ID: FM0070121

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Abstract

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.

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© The Japanese Pharmacological Society 2008
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