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Neuropsychotoxicity of abused drugs: effects of serotonin receptor ligands on methamphetamine- and cocaine-induced behavioral sensitization in mice Ago Y; Nakamura S; Baba A; Matsuda TJ Pharmacol Sci 2008[Jan]; 106 (1): 15-21Repeated 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-HT(1A)-receptor agonist, and ritanserin, a 5-HT(2)-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-HT(3)-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-HT(1A)-receptor agonists and 5-HT(2)-receptor antagonists may have a potential therapeutic value for the treatment of methamphetamine abuse or psychosis.|Amphetamine-Related Disorders/*drug therapy/metabolism/psychology[MESH]|Animals[MESH]|Behavior, Animal/*drug effects[MESH]|Brain/*drug effects/metabolism[MESH]|Bridged Bicyclo Compounds, Heterocyclic/pharmacology[MESH]|Central Nervous System Stimulants/*toxicity[MESH]|Cocaine-Related Disorders/*drug therapy/metabolism/psychology[MESH]|Cocaine/*toxicity[MESH]|Dioxanes/pharmacology[MESH]|Dioxoles/pharmacology[MESH]|Disease Models, Animal[MESH]|Ligands[MESH]|Methamphetamine/*toxicity[MESH]|Mice[MESH]|Motor Activity/drug effects[MESH]|Oxazines/pharmacology[MESH]|Receptors, Serotonin/*drug effects/metabolism[MESH]|Ritanserin/pharmacology[MESH]|Serotonin 5-HT1 Receptor Agonists[MESH]|Serotonin 5-HT2 Receptor Antagonists[MESH]|Serotonin 5-HT3 Receptor Antagonists[MESH]|Serotonin Agents/*pharmacology/therapeutic use[MESH]|Serotonin Antagonists/pharmacology[MESH]|Serotonin Receptor Agonists/pharmacology[MESH]|Serotonin/metabolism[MESH] |
