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Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat.

Abstract

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.

Authors+Show Affiliations

Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24121061

Citation

Cox, Brittney M., et al. "Behavioral and Neurochemical Effects of Repeated MDMA Administration During Late Adolescence in the Rat." Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 48, 2014, pp. 229-35.
Cox BM, Shah MM, Cichon T, et al. Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat. Prog Neuropsychopharmacol Biol Psychiatry. 2014;48:229-35.
Cox, B. M., Shah, M. M., Cichon, T., Tancer, M. E., Galloway, M. P., Thomas, D. M., & Perrine, S. A. (2014). Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat. Progress in Neuro-psychopharmacology & Biological Psychiatry, 48, pp. 229-35. doi:10.1016/j.pnpbp.2013.09.021.
Cox BM, et al. Behavioral and Neurochemical Effects of Repeated MDMA Administration During Late Adolescence in the Rat. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jan 3;48:229-35. PubMed PMID: 24121061.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat. AU - Cox,Brittney M, AU - Shah,Mrudang M, AU - Cichon,Teri, AU - Tancer,Manuel E, AU - Galloway,Matthew P, AU - Thomas,David M, AU - Perrine,Shane A, Y1 - 2013/10/10/ PY - 2013/07/12/received PY - 2013/09/27/revised PY - 2013/09/29/accepted PY - 2013/10/15/entrez PY - 2013/10/15/pubmed PY - 2014/8/2/medline KW - 3,4-methylenedioxymethamphetamine KW - 5-HIAA KW - 5-HT serotonin KW - 5-hydroxyindoleacetic acid KW - 5-hydroxytryptamine KW - ANOVA KW - Amygdala KW - Anxiety KW - Conditioned place preference KW - Dorsal raphe KW - HPLC KW - High Pressure Liquid Chromatography KW - IP KW - Intraperitoneal KW - MDMA KW - PND KW - SEM KW - SERT KW - Serotonin KW - analysis of variance KW - postnatal date KW - serotonin transporter KW - standard error of the mean SP - 229 EP - 35 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog. Neuropsychopharmacol. Biol. Psychiatry VL - 48 N2 - 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. SN - 1878-4216 UR - https://www.unboundmedicine.com/medline/citation/24121061/Behavioral_and_neurochemical_effects_of_repeated_MDMA_administration_during_late_adolescence_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(13)00217-0 DB - PRIME DP - Unbound Medicine ER -