Fujii Harumi, Ishihama Toshihiro, Ago Yukio, Shintani Norihito, Kakuda Michiya, Hashimoto Hitoshi, Baba Akemichi, Matsuda Toshio
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Peptides. 2007 Sep;28(9):1674-9. doi: 10.1016/j.peptides.2007.06.012. Epub 2007 Jun 19.
Mice lacking the PACAP gene (PACAP(-/-)) display psychomotor abnormalities such as novelty-induced hyperactivity and jumping behavior, and they show different responses to amphetamine, a typical psychostimulant. The present study examined the possible role of endogenous PACAP in methamphetamine (METH)-induced hyperactivity and behavioral sensitization. The locomotor activity of hyperactive PACAP(-/-) mice was measured using the infrared photocell beam detection system, Acti-Track, after a habituation period. Single administration of METH (1 and 2mg/kg) caused a robust increase in locomotor activity of mice, but this effect did not differ between wild-type and PACAP(-/-) mice. Repeated administration of METH (1mg/kg) for 7 days enhanced METH-induced hyperactivity, and this sensitization was observed even when withdrawn for 7 days. There was no difference in the degree of development and expression of METH-induced behavioral sensitization between wild-type and PACAP(-/-) mice. In addition, there was no difference in METH-induced increases in extracellular serotonin and dopamine levels in the prefrontal cortex of the normal and sensitized mice between the two groups. These results suggest that endogenous PACAP is not involved in the locomotor stimulant activity of acute METH and repeated METH-induced behavioral and neurochemical sensitization.
缺乏垂体腺苷酸环化酶激活肽基因（PACAP(-/-)）的小鼠表现出精神运动异常，如新奇诱导的多动和跳跃行为，并且它们对典型精神兴奋剂苯丙胺表现出不同反应。本研究考察了内源性PACAP在甲基苯丙胺（METH）诱导的多动和行为敏化中的可能作用。在适应期后，使用红外光电管光束检测系统Acti-Track测量多动的PACAP(-/-)小鼠的自发活动。单次给予METH（1和2mg/kg）可使小鼠的自发活动显著增加，但野生型和PACAP(-/-)小鼠之间的这种效应没有差异。重复给予METH（1mg/kg）7天可增强METH诱导的多动，并且即使停药7天也能观察到这种敏化现象。野生型和PACAP(-/-)小鼠之间METH诱导的行为敏化的发展程度和表达没有差异。此外，两组正常和敏化小鼠前额叶皮质中METH诱导的细胞外5-羟色胺和多巴胺水平升高也没有差异。这些结果表明，内源性PACAP不参与急性METH的运动刺激活性以及重复METH诱导的行为和神经化学敏化。
