PMID- 16483555 OWN - NLM STAT- MEDLINE DCOM- 20060726 LR - 20181113 IS - 0006-8993 (Print) IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1077 IP - 1 DP - 2006 Mar 10 TI - Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPgammaS binding in adult rats. PG - 178-86 AB - Recreational use of methylenedioxymethamphetamine (MDMA) has dramatically increased among juveniles and young adults of child-bearing age, and the potential for fetal exposure has increased. For this reason, it is surprising that comparatively few studies have assessed the long-term impact of early MDMA exposure on serotonin (5-HT) and dopamine (DA) neurotransmitter systems. The purpose of this study was to determine whether repeated exposure to MDMA during the preweanling period would cause long-term changes in 5-HT and DA functioning. Rats were treated with saline or 20 mg/kg MDMA (two injections per day) from postnatal day (PD) 11-20. At PD 90, rats were killed, and their dorsal striatum, prefrontal cortex, and hippocampus were removed. 5-HT and DA content, as well as their metabolites, were measured using HPLC. In addition, cAMP-dependent protein kinase A (PKA) activity and agonist-stimulated [35S]GTPgammaS binding was assayed using tissue homogenates from each brain region. Results indicated that early MDMA exposure caused a decrease in PKA activity and 5-HT content in the prefrontal cortex and hippocampus while increasing the efficacy of 5-HT1A receptors as measured by agonist-stimulated [35S]GTPgammaS binding. Additionally, DA content was reduced in the dorsal striatum and prefrontal cortex. These data indicate that early MDMA exposure has long-term effects on the 5-HT and DA neurotransmitter systems that may be mediated, at least partially, by changes in 5-HT1A receptor sensitivity. FAU - Crawford, Cynthia A AU - Crawford CA AD - Department of Psychology, California State University, San Bernardino, CA 92407, USA. ccrawfor@csusb.edu FAU - Williams, Michael T AU - Williams MT FAU - Kohutek, Jodie L AU - Kohutek JL FAU - Choi, Fiona Y AU - Choi FY FAU - Yoshida, Shelly T AU - Yoshida ST FAU - McDougall, Sanders A AU - McDougall SA FAU - Vorhees, Charles V AU - Vorhees CV LA - eng GR - K01 DA014269-05/DA/NIDA NIH HHS/United States GR - R01 DA021394-02/DA/NIDA NIH HHS/United States GR - DA006733/DA/NIDA NIH HHS/United States GR - K01 DA014269/DA/NIDA NIH HHS/United States GR - R01 DA021394/DA/NIDA NIH HHS/United States GR - R01 DA006733/DA/NIDA NIH HHS/United States GR - DA014269/DA/NIDA NIH HHS/United States GR - R01 DA006733-17/DA/NIDA NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060214 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Hallucinogens) RN - 102-32-9 (3,4-Dihydroxyphenylacetic Acid) RN - 333DO1RDJY (Serotonin) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - VTD58H1Z2X (Dopamine) SB - IM MH - 3,4-Dihydroxyphenylacetic Acid/metabolism MH - Age Factors MH - Animals MH - Animals, Newborn MH - Brain/cytology/*drug effects/enzymology MH - Cyclic AMP-Dependent Protein Kinases/*drug effects MH - Dopamine/*metabolism MH - Female MH - Follow-Up Studies MH - Guanosine 5'-O-(3-Thiotriphosphate)/*metabolism MH - Hallucinogens/pharmacology MH - Hippocampus/cytology/drug effects/enzymology MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Neurons/*drug effects/enzymology MH - Prosencephalon/cytology/drug effects/enzymology MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/*metabolism MH - Sex Factors PMC - PMC2888305 MID - NIHMS207856 EDAT- 2006/02/18 09:00 MHDA- 2006/07/27 09:00 PMCR- 2010/06/21 CRDT- 2006/02/18 09:00 PHST- 2005/10/21 00:00 [received] PHST- 2005/12/30 00:00 [revised] PHST- 2006/01/06 00:00 [accepted] PHST- 2006/02/18 09:00 [pubmed] PHST- 2006/07/27 09:00 [medline] PHST- 2006/02/18 09:00 [entrez] PHST- 2010/06/21 00:00 [pmc-release] AID - S0006-8993(06)00083-7 [pii] AID - 10.1016/j.brainres.2006.01.017 [doi] PST - ppublish SO - Brain Res. 2006 Mar 10;1077(1):178-86. doi: 10.1016/j.brainres.2006.01.017. Epub 2006 Feb 14.