Iyo M, Bi Y, Hashimoto K, Inada T, Fukui S
Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan.
Eur J Pharmacol. 1996 Sep 26;312(2):163-70. doi: 10.1016/0014-2999(96)00479-7.
Effects of an interaction between rolipram, a cyclic adenosine 3', 5'-monophosphate (cyclic AMP) phosphodiesterase inhibitor, and methamphetamine on the development of behavioral sensitization were observed in rats. In vivo microdialysis showed that a single dose of 4 mg/kg methamphetamine (i.p.) significantly increased striatal dopamine levels while coadministration with 4 mg/kg rolipram (i.p.) did not affect these levels. Also, methamphetamine alone did not alter striatal cyclic AMP levels but coadministration with rolipram and rolipram alone significantly increased these levels. The administration of 4 mg/kg methamphetamine (i.p.) once a day for 5 days significantly enhanced hyperlocomotion and rearing induced by a 2-mg/kg methamphetamine challenge (i.p.) after a 1-week withdrawal period, compared with controls or coadministration with 4 mg/kg rolipram (i.p.). Striatal dopamine levels, detected by in vivo microdialysis, were increased following the challenge but were comparable between the groups. These findings suggest that rolipram prevents methamphetamine-induced behavioral sensitization by increasing cyclic AMP levels while not affecting dopamine-releasing processes.
在大鼠中观察了环磷腺苷（cAMP）磷酸二酯酶抑制剂咯利普兰与甲基苯丙胺之间的相互作用对行为敏化发展的影响。体内微透析显示，单剂量4mg/kg甲基苯丙胺（腹腔注射）可显著提高纹状体多巴胺水平，而与4mg/kg咯利普兰（腹腔注射）共同给药则不影响这些水平。此外，单独使用甲基苯丙胺不会改变纹状体cAMP水平，但与咯利普兰共同给药以及单独使用咯利普兰均会显著提高这些水平。与对照组或与4mg/kg咯利普兰（腹腔注射）共同给药相比，每天一次腹腔注射4mg/kg甲基苯丙胺，连续5天，在停药1周后，可显著增强2mg/kg甲基苯丙胺（腹腔注射）激发引起的运动亢进和竖毛反应。通过体内微透析检测，激发后纹状体多巴胺水平升高，但各组之间相当。这些发现表明，咯利普兰通过提高cAMP水平来预防甲基苯丙胺诱导的行为敏化，而不影响多巴胺释放过程。
