PMID- 26612383 OWN - NLM STAT- MEDLINE DCOM- 20161027 LR - 20200825 IS - 1873-7862 (Electronic) IS - 0924-977X (Linking) VI - 26 IP - 1 DP - 2016 Jan TI - Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[(1)(8)F]-ADAM/small-animal PET study. PG - 92-104 LID - S0924-977X(15)00351-X [pii] LID - 10.1016/j.euroneuro.2015.11.001 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier B.V. and ECNP. All rights reserved. FAU - Shih, Jui-Hu AU - Shih JH AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. FAU - Ma, Kuo-Hsing AU - Ma KH AD - Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. FAU - Chen, Chien-Fu F AU - Chen CF AD - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. FAU - Cheng, Cheng-Yi AU - Cheng CY AD - Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. FAU - Pao, Li-Heng AU - Pao LH AD - School of Pharmacy, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Health-Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan. FAU - Weng, Shao-Ju AU - Weng SJ AD - Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. FAU - Huang, Yuahn-Sieh AU - Huang YS AD - Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. FAU - Shiue, Chyng-Yann AU - Shiue CY AD - Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. FAU - Yeh, Ming-Kung AU - Yeh MK AD - School of Pharmacy, National Defense Medical Center, Taipei, Taiwan; Ministry of Health and Welfare, Taiwan. FAU - Li, I-Hsun AU - Li IH AD - Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. Electronic address: lhs01077@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151114 PL - Netherlands TA - Eur Neuropsychopharmacol JT - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JID - 9111390 RN - 0 (Benzylamines) RN - 0 (Fluorine Radioisotopes) RN - 0 (N,N-dimethyl-2-(2-amino-4-fluorophenylthio)benzylamine) RN - 0 (Neuroprotective Agents) RN - 0 (RNA-Binding Proteins) RN - 0 (Radiopharmaceuticals) RN - 0 (Serotonin Agents) RN - 0 (Sert1 protein, rat) RN - 0 (Stilbenes) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - Q369O8926L (Resveratrol) RN - W980KJ009P (Corticosterone) SB - IM MH - Animals MH - Benzylamines MH - Brain/diagnostic imaging/*drug effects/*metabolism MH - Brain Mapping MH - Corticosterone/blood MH - Depressive Disorder/diagnostic imaging/drug therapy/metabolism MH - Dose-Response Relationship, Drug MH - Fluorine Radioisotopes MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity MH - Neuroprotective Agents/*pharmacology MH - Positron-Emission Tomography MH - RNA-Binding Proteins/*metabolism MH - Radiopharmaceuticals MH - Random Allocation MH - Rats, Sprague-Dawley MH - Resveratrol MH - Serotonin Agents/toxicity MH - Stilbenes/*pharmacology OTO - NOTNLM OT - 4-[(18)F]-ADAM OT - MDMA OT - Occupancy OT - Resveratrol OT - Serotonin transporter OT - Small-animal PET EDAT- 2015/11/28 06:00 MHDA- 2016/11/01 06:00 CRDT- 2015/11/28 06:00 PHST- 2015/04/11 00:00 [received] PHST- 2015/10/23 00:00 [revised] PHST- 2015/11/08 00:00 [accepted] PHST- 2015/11/28 06:00 [entrez] PHST- 2015/11/28 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] AID - S0924-977X(15)00351-X [pii] AID - 10.1016/j.euroneuro.2015.11.001 [doi] PST - ppublish SO - Eur Neuropsychopharmacol. 2016 Jan;26(1):92-104. doi: 10.1016/j.euroneuro.2015.11.001. Epub 2015 Nov 14.