PMID- 12480182 OWN - NLM STAT- MEDLINE DCOM- 20030616 LR - 20190826 IS - 0169-328X (Print) IS - 0169-328X (Linking) VI - 108 IP - 1-2 DP - 2002 Dec TI - Synaptotagmin I and IV are differentially regulated in the brain by the recreational drug 3,4-methylenedioxymethamphetamine (MDMA). PG - 94-101 AB - 3,4-Methylenedioxymethamphetamine (MDMA or Ecstasy) is a widely abused drug. In brains of mice exposed to MDMA, we recently detected altered expression of several cDNAs and genes by using the differential display polymerase chain reaction (PCR) method. Expression of one such cDNA, which exhibited 98% sequence homology with the synaptic vesicle protein synaptotagmin IV, decreased 2 h after MDMA treatment. Herein, the effect of MDMA on expression of both synaptotagmin I and IV was studied in detail, since the two proteins are functionally interrelated. PCR analyses (semi-quantitative and real-time) confirmed that upon treatment with MDMA, expression of synaptotagmin IV decreased both in the midbrain and frontal cortex of mice. Decreases in the protein levels of synaptotagmin IV were confirmed by Western immunoblotting with anti-synaptotagmin IV antibodies. In contrast, the same exposure to MDMA increased expression of synaptotagmin I in the midbrain, a region rich in serotonergic neurons, but not in the frontal cortex. This differential expression was confirmed at the protein level with anti-synaptotagmin I antibodies. MDMA did not induce down- or up-regulation of synaptotagmin IV and I, respectively, in serotonin transporter knockout mice (-/-) that are not sensitive to MDMA. Therefore, psychoactive drugs, such as MDMA, appear to modulate expression of synaptic vesicle proteins, and possibly vesicle trafficking, in the brain. FAU - Peng, Weiping AU - Peng W AD - Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. FAU - Premkumar, Arumugam AU - Premkumar A FAU - Mossner, Rainald AU - Mossner R FAU - Fukuda, Mitsunori AU - Fukuda M FAU - Lesch, K Peter AU - Lesch KP FAU - Simantov, Rabi AU - Simantov R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Brain Res Mol Brain Res JT - Brain research. Molecular brain research JID - 8908640 RN - 0 (Calcium-Binding Proteins) RN - 0 (Carrier Proteins) RN - 0 (Hallucinogens) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) RN - 0 (SLC6A4 protein, human) RN - 0 (SYT1 protein, human) RN - 0 (SYT4 protein, human) RN - 0 (Serotonin Agents) RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - 0 (Slc6a4 protein, mouse) RN - 0 (Synaptotagmin I) RN - 0 (Syt1 protein, mouse) RN - 0 (Syt4 protein, mouse) RN - 134193-27-4 (Synaptotagmins) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Brain/*drug effects/*metabolism MH - *Calcium-Binding Proteins MH - Carrier Proteins/genetics/metabolism MH - Down-Regulation/physiology MH - Hallucinogens MH - Humans MH - Male MH - Membrane Glycoproteins/genetics/*metabolism MH - *Membrane Transport Proteins MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Nerve Tissue Proteins/genetics/*metabolism MH - RNA, Messenger/metabolism MH - Serotonin Agents/*pharmacology MH - Serotonin Plasma Membrane Transport Proteins MH - Synaptotagmin I MH - Synaptotagmins EDAT- 2002/12/14 04:00 MHDA- 2003/06/17 05:00 CRDT- 2002/12/14 04:00 PHST- 2002/12/14 04:00 [pubmed] PHST- 2003/06/17 05:00 [medline] PHST- 2002/12/14 04:00 [entrez] AID - S0169328X02005181 [pii] AID - 10.1016/s0169-328x(02)00518-1 [doi] PST - ppublish SO - Brain Res Mol Brain Res. 2002 Dec;108(1-2):94-101. doi: 10.1016/s0169-328x(02)00518-1.