Modification of cocaine-induced behavioral and neurochemical effects by serotonin1A receptor agonist/antagonist in mice.
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.
Nakamura
Shigeo
S
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Ago
Yukio
Y
Hayashi
Aiko
A
Itoh
Soichi
S
Kakuda
Michiya
M
Hashimoto
Hitoshi
H
Baba
Akemichi
A
Matsuda
Toshio
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine