| Summary: | 博士 === 國防醫學院 === 醫學科學研究所 === 104 === 3,4-methylenedioxymethamphetamine (MDMA) is a widely misused drug that has been reported to evoke acute weight loss and hypothalamic-pituitary-adrenal axis activation, but also induces long-term psychophysiological changes in rodents, promoting depressive-like behavior and reducing the density of brain serotonin transporters (SERT). Resveratrol (RSV) is a natural polyphenolic phytoalexin and known for its antioxidant, antidepressant, and neuroprotective effects. However, biological targets of RSV as well as its neuroprotective effects against MDMA are still poorly understood. In this study, we examined binding potency of RSV and MDMA to SERT using small-animal positron emission tomography (PET) with the SERT radioligand, N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) and investigated the protection of RSV against the acute and long-term adverse effects of MDMA. RSV was found to exhibit binding potentials to SERT in vivo in a dose-dependent manner with variation among brain regions. To assess the protection by RSV against the acute and long-term adverse effects of MDMA, we injected animals with RSV (20 mg/kg, i.p.) and MDMA (10 mg/kg, s.c.) twice daily for 4 consecutive days. Small-animal PET imaging data showed that RSV protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus 2 weeks following the co-treatment. RSV also prevented the MDMA-evoked increase in immobility in the forced swim test. Remarkably, RSV inhibited the MDMA-induced elevation in plasma corticosterone. Together, these findings suggest that RSV is not only a potential antidepressant, but that it also confers protection against the neurobiological and behavioral effects of MDMA.
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