Division of Psychobiology, Tokyo Institute of Psychiatry, Tokyo, Japan.
Curr Neuropharmacol. 2011 Mar;9(1):73-8. doi: 10.2174/157015911795017056.
Previously, we found fluoxetine reduces methamphetamine preference in mice. However, effects of fluoxetine on developed methamphetamine preference and on methamphetamine induced gene expression changes have been largely unknown. The present study investigates effects of post-treatment with fluoxetine on methamphetamine dependence and on gene expressions after long-term withdrawal in mice. First, we examined whether chronic post-treatment with fluoxetine attenuated methamphetamine-conditioned place preference. Next, we examined the changes in gene expression levels after long-term withdrawal (with saline or fluoxetine treatment) following chronic methamphetamine treatment. Using mRNA from the pooled frontal cortices of 10 mice per group, gene expression analyses were performed using a custom-developed cDNA array and a real-time quantitative reverse transcription-PCR. Chronic post-treatments with fluoxetine abolished the conditioned place preference developed by methamphetamine administrations. Even after long-term withdrawal from repeated methamphetamine administration, µ-opioid receptor (MOP) gene expression was significantly reduced in the frontal cortex. The reduced MOP gene expression in the frontal cortex was restored by chronic administration with fluoxetine. These changes were confirmed by Western blot analyses. These findings suggest that the chronic post-treatments with fluoxetine might be effective for restoring the reduction of MOP levels in the frontal cortex following long-term abstinence from methamphetamine.
先前，我们发现氟西汀可减少小鼠对甲基苯丙胺的偏好。然而，氟西汀对已形成的甲基苯丙胺偏好和对甲基苯丙胺诱导的基因表达变化的影响在很大程度上尚未可知。本研究调查了氟西汀的后期治疗对小鼠长期戒断后甲基苯丙胺依赖和基因表达的影响。首先，我们检查了慢性氟西汀后期治疗是否减弱了甲基苯丙胺条件性位置偏好。接下来，我们检查了慢性甲基苯丙胺治疗后长期戒断（用生理盐水或氟西汀治疗）后基因表达水平的变化。使用每组 10 只小鼠的前额皮质混合 mRNA，使用定制的 cDNA 阵列和实时定量逆转录-PCR 进行基因表达分析。慢性氟西汀后期治疗消除了甲基苯丙胺给药引起的条件性位置偏好。即使在反复甲基苯丙胺给药后长期戒断后，前额皮质中的μ-阿片受体（MOP）基因表达也显著降低。慢性氟西汀给药可恢复前额皮质中 MOP 基因表达的减少。这些变化通过 Western blot 分析得到证实。这些发现表明，慢性氟西汀后期治疗可能有助于恢复长期戒断后前额皮质中 MOP 水平的降低。
