Etou K, Kuroki T, Kawahara T, Yonezawa Y, Tashiro N, Uchimura H
Department of Neuropsychiatry, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Pharmacol Biochem Behav. 1998 Dec;61(4):427-34. doi: 10.1016/s0091-3057(98)00128-2.
Phencyclidine (PCP; 5.0 mg/kg, i.p.) produced a greater increase in extracellular dopamine (DA) levels in the prefrontal cortex than in the striatum, while PCP increased the extracellular 5-hydroxytryptamine (serotonin; 5-HT) levels in the prefrontal cortex but not the striatum, as determined by in vivo microdialysis in awake, freely moving rats. The cholecystokinin (CCK)-related decapeptide ceruletide (120 and 400 microg/kg, i.p.), administered 60 min prior to PCP, significantly attenuated the PCP-induced increase in the extracellular levels of DA and 5-HT in the prefrontal cortex, but not in the striatum. These effects were reversed by PD 135,158, a selective CCK-B receptor antagonist (0.1 mg/kg, s.c.), administered 5 min prior to ceruletide. When administered alone, ceruletide (400 microg/kg, i.p.) significantly increased basal extracellular DA levels only in the prefrontal cortex. The selective N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (0.5 mg/kg, i.p.) also increased extracellular DA levels in the prefrontal cortex, but this effect was unaffected by ceruletide pretreatment. These results suggest that ceruletide may differentially modulate basal and PCP-induced release of DA and 5-HT in the prefrontal cortex.
在清醒、自由活动的大鼠中通过体内微透析测定发现，苯环利定（PCP；5.0毫克/千克，腹腔注射）使前额叶皮质细胞外多巴胺（DA）水平的升高幅度大于纹状体，而PCP增加了前额叶皮质细胞外5-羟色胺（血清素；5-HT）水平，但未增加纹状体中的该水平。在PCP给药前60分钟腹腔注射胆囊收缩素（CCK）相关的十肽蛙皮素（120和400微克/千克），可显著减弱PCP诱导的前额叶皮质细胞外DA和5-HT水平的升高，但对纹状体无此作用。在蛙皮素给药前5分钟皮下注射选择性CCK-B受体拮抗剂PD 135,158（0.1毫克/千克）可逆转这些作用。单独给药时，蛙皮素（400微克/千克，腹腔注射）仅显著增加前额叶皮质的基础细胞外DA水平。选择性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂地佐环平（0.5毫克/千克，腹腔注射）也增加了前额叶皮质的细胞外DA水平，但该作用不受蛙皮素预处理的影响。这些结果表明，蛙皮素可能对前额叶皮质中基础的以及PCP诱导的DA和5-HT释放进行差异性调节。
