Neuropsychotoxicity of abused drugs: effects of serotonin receptor ligands on methamphetamine- and cocaine-induced behavioral sensitization in mice.
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-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.
Ago
Yukio
Y
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Nakamura
Shigeo
S
Baba
Akemichi
A
Matsuda
Toshio
T
D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D004146:Dioxanes / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004195:Disease Models, Animal; D008024:Ligands; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010078:Oxazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D018490:Serotonin Agents / Q000494:pharmacology* / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D000697:Central Nervous System Stimulants; D004146:Dioxanes; D004149:Dioxoles; D008024:Ligands; D010078:Oxazines; D011985:Receptors, Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; D012701:Serotonin; D008694:Methamphetamine; C070671:azasetron; D003042:Cocaine; C096294:osemozotan