Abstract
Administration of cocaine causes a locomotor stimulant effect and increases extracellular levels of serotonin (5-HT) and dopamine (DA) in the brains of rodents. Previous studies show that 5-HT1A receptor agonist and antagonist modify the cocaine-induced behavioral and neurochemical effects in the rats. However, the role of the 5-HT system on the effects of cocaine has not been studied in the prefrontal cortex. The present study examined in ddY-strain male mice the effects of the 5-HT1A receptor agonist osemozotan and the receptor antagonist WAY100635 on cocaine-induced locomotor stimulant effect and increases in extracellular levels of 5-HT and DA in the prefrontal cortex. The cocaine-induced locomotor stimulant effect was attenuated by osemozotan and enhanced by WAY100635. The cocaine-induced increase in extracellular levels of 5-HT was attenuated by osemozotan, and enhanced by WAY100635. The cocaine-induced increase in extracellular levels of DA was enhanced by osemozotan, but not affected by WAY100635. These results suggest that the prefrontal 5-HT system plays a pivotal role in the locomotor stimulant effect of cocaine in mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Behavior, Animal / drug effects*
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Behavior, Animal / physiology
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Brain / drug effects*
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Brain / metabolism
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Cocaine / antagonists & inhibitors*
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Cocaine / metabolism
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Cocaine-Related Disorders / drug therapy
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Cocaine-Related Disorders / metabolism*
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Cocaine-Related Disorders / physiopathology
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Disease Models, Animal
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Dopamine / metabolism
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Dopamine Uptake Inhibitors / antagonists & inhibitors
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Dopamine Uptake Inhibitors / metabolism
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Dose-Response Relationship, Drug
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Drug Interactions / physiology
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Extracellular Fluid / drug effects
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Extracellular Fluid / metabolism
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Male
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Mice
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Motor Activity / drug effects
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Motor Activity / physiology
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Prefrontal Cortex / drug effects
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Prefrontal Cortex / metabolism
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Receptor, Serotonin, 5-HT1A / drug effects*
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Receptor, Serotonin, 5-HT1A / metabolism
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Serotonin / metabolism
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Serotonin Agents / pharmacology*
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Serotonin Antagonists / pharmacology
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Serotonin Receptor Agonists / pharmacology
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Time Factors
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Up-Regulation / drug effects
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Up-Regulation / physiology
Substances
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Dopamine Uptake Inhibitors
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Serotonin Agents
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Serotonin Antagonists
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Serotonin Receptor Agonists
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Receptor, Serotonin, 5-HT1A
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Serotonin
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Cocaine
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Dopamine