Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study.
Jui-Hu Shih, Kuo-Hsing Ma, Chien-Fu F Chen, Cheng-Yi Cheng, Li-Heng Pao, Shao-Ju Weng, Yuahn-Sieh Huang, Chyng-Yann Shiue, Ming-Kung Yeh, I-Hsun Li
European Neuropsychopharmacology January 2016 DOI: 10.1016/j.euroneuro.2015.11.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Resveratrol MDMA |
| Dose | MDMA 10 mg/kg s.c.; resveratrol 20 mg/kg i.p. twice daily |
| Duration | 4 consecutive days of co-treatment; follow-up 2 weeks after |
| Measures | 4-[(18)F]-ADAM PET, plasma corticosterone, forced swim test |
| Topics | MDMA |
| Keywords | 4-18f-adam Occupancy Resveratrol Serotonin transporter Small-Animal PET |
| Key points | Resveratrol bound SERT in vivo in a dose-dependent manner and, co-administered with MDMA (20 mg/kg twice daily for 4 days), significantly reduced MDMA-induced acute plasma corticosterone elevation. Two weeks after co-treatment, PET showed resveratrol protected against MDMA-induced SERT reduction in the midbrain and thalamus, and forced swim test results indicated it ameliorated depressive-like behaviors. The authors suggest resveratrol is a potential antidepressant and may protect against MDMA-induced neurobiological and behavioral changes. |
Abstract
The misuse of 3,4-methylenedioxymethamphetamine (MDMA) has drawn a growing concern worldwide for its psychophysiological impacts on humans. MDMA abusers are often accompanied by long-term serotonergic neurotoxicity, which is associated with reduced density of cerebral serotonin transporters (SERT) and depressive disorders. Resveratrol (RSV) is a natural polyphenolic phytoalexin that has been known for its antidepressant and neuroprotective effects. However, biological targets of RSV as well as its neuroprotective effects against MDMA remained largely unknown. 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-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) and investigated the protection of RSV against the acute and long-term adverse effects of MDMA. We found that RSV exhibit binding potentials to SERT in vivo in a dose-dependent manner with variation among brain regions. When the MDMA-treated rats (10mg/kg, s.c.) were co-injected with RSV (20mg/kg, i.p.) twice daily for 4 consecutive days, MDMA-induced acute elevation in plasma corticosterone was significantly reduced. Further, 4-[(18)F]-ADAM PET imaging revealed that RSV protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus 2 weeks following the co-treatment. The PET data were comparable to the observation from the forced swim test that RSV sufficiently ameliorated the depressive-like behaviors of the MDMA-treated rats. Together, these findings suggest that RSV is a potential antidepressant and may confer protection against neurobiological and behavioral changes induced by MDMA.
Comparable studies
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- Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[18F]-ADAM PET Imaging International Journal of Molecular Sciences June 24, 2022
- MDMA and memory, addiction, and depression: dose-effect analysis Psychopharmacology March 1, 2022
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