PMID- 24121061 OWN - NLM STAT- MEDLINE DCOM- 20140801 LR - 20211021 IS - 1878-4216 (Electronic) IS - 0278-5846 (Print) IS - 0278-5846 (Linking) VI - 48 DP - 2014 Jan 3 TI - Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat. PG - 229-35 LID - S0278-5846(13)00217-0 [pii] LID - 10.1016/j.pnpbp.2013.09.021 [doi] AB - Adolescents and young adults disproportionately abuse 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy'); however, since most MDMA research has concentrated on adults, the effects of MDMA on the developing brain remain obscure. Therefore, we evaluated place conditioning to MDMA (or saline) during late adolescence and assessed anxiety-like behavior and monoamine levels during abstinence. Rats were conditioned to associate 5 or 10mg/kg MDMA or saline with contextual cues over 4 twice-daily sessions. Five days after conditioning, anxiety-like behavior was examined with the open field test and brain tissue was collected to assess serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal raphe, amygdala, and hippocampus by high-pressure liquid chromatography (HPLC). In a separate group of rats, anxiety-like and avoidant behaviors were measured using the light-dark box test under similar experimental conditions. MDMA conditioning caused a place aversion at 10, but not at 5, mg/kg, as well as increased anxiety-like behavior in the open field and avoidant behavior in light-dark box test at the same dose. Additionally, 10mg/kg MDMA decreased 5-HT in the dorsal raphe, increased 5-HT and 5-HIAA in the amygdala, and did not alter levels in the hippocampus. Overall, we show that repeated high (10mg/kg), but not low (5mg/kg), dose MDMA during late adolescence in rats increases anxiety-like and avoidant behaviors, accompanied by region-specific alterations in 5-HT levels during abstinence. These results suggest that MDMA causes a region-specific dysregulation of the serotonin system during adolescence that may contribute to maladaptive behavior. CI - (c) 2013. FAU - Cox, Brittney M AU - Cox BM AD - Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA. FAU - Shah, Mrudang M AU - Shah MM FAU - Cichon, Teri AU - Cichon T FAU - Tancer, Manuel E AU - Tancer ME FAU - Galloway, Matthew P AU - Galloway MP FAU - Thomas, David M AU - Thomas DM FAU - Perrine, Shane A AU - Perrine SA LA - eng GR - K01 DA024760/DA/NIDA NIH HHS/United States PT - Journal Article DEP - 20131010 PL - England TA - Prog Neuropsychopharmacol Biol Psychiatry JT - Progress in neuro-psychopharmacology & biological psychiatry JID - 8211617 RN - 0 (Hallucinogens) RN - 333DO1RDJY (Serotonin) RN - 54-16-0 (Hydroxyindoleacetic Acid) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Adaptation, Ocular/drug effects MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - Behavior, Animal/*drug effects MH - Brain/*drug effects/*metabolism MH - Chromatography, High Pressure Liquid MH - Conditioning, Operant/drug effects MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Exploratory Behavior/drug effects MH - Hallucinogens/*administration & dosage MH - Hydroxyindoleacetic Acid/metabolism MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/metabolism MH - Time Factors PMC - PMC4348097 MID - NIHMS667152 OTO - NOTNLM OT - 3,4-methylenedioxymethamphetamine OT - 5-HIAA OT - 5-HT serotonin OT - 5-hydroxyindoleacetic acid OT - 5-hydroxytryptamine OT - ANOVA OT - Amygdala OT - Anxiety OT - Conditioned place preference OT - Dorsal raphe OT - HPLC OT - High Pressure Liquid Chromatography OT - IP OT - Intraperitoneal OT - MDMA OT - PND OT - SEM OT - SERT OT - Serotonin OT - analysis of variance OT - postnatal date OT - serotonin transporter OT - standard error of the mean EDAT- 2013/10/15 06:00 MHDA- 2014/08/02 06:00 PMCR- 2015/03/03 CRDT- 2013/10/15 06:00 PHST- 2013/07/12 00:00 [received] PHST- 2013/09/27 00:00 [revised] PHST- 2013/09/29 00:00 [accepted] PHST- 2013/10/15 06:00 [entrez] PHST- 2013/10/15 06:00 [pubmed] PHST- 2014/08/02 06:00 [medline] PHST- 2015/03/03 00:00 [pmc-release] AID - S0278-5846(13)00217-0 [pii] AID - 10.1016/j.pnpbp.2013.09.021 [doi] PST - ppublish SO - Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jan 3;48:229-35. doi: 10.1016/j.pnpbp.2013.09.021. Epub 2013 Oct 10.