PMID- 23246480 OWN - NLM STAT- MEDLINE DCOM- 20131025 LR - 20131121 IS - 1879-3185 (Electronic) IS - 0300-483X (Linking) VI - 311 IP - 1-2 DP - 2013 Sep 6 TI - Sex-dependent effects of early maternal deprivation on MDMA-induced conditioned place preference in adolescent rats: possible neurochemical correlates. PG - 78-86 LID - S0300-483X(12)00422-2 [pii] LID - 10.1016/j.tox.2012.12.003 [doi] AB - The early neonatal stage constitutes a sensitive period during which exposure to adverse events can increase the risk of neuropsychiatric disorders. Maternal deprivation (MD) is a model of early life stress that induces long-term behavioural and physiological alterations, including susceptibility to different drugs of abuse. In the present study we have used the conditioned place preference (CPP) paradigm to address the influence of MD on the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA) in adolescent animals of both sexes. We have previously observed in adolescent rats that MD induces modifications in the serotonergic and endocannabinoid systems, which play a role in the rewarding effects of MDMA. In light of this evidence, we hypothesized that MD would alter the psychobiological consequences of exposure to MDMA. Neonatal Wistar rats underwent MD (24h, on PND 9) or were left undisturbed (controls). The animals were conditioned with 2.5mg/kg MDMA during the periadolescent period (PND 34-PND 43) and were tested in the open-field test at the end of adolescence (PND 60). Animals were sacrificed on PND 68-75 and levels of serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid were measured in the striatum, hippocampus and cortex, while the expression of hippocampal CB1 cannabinoid receptor (CB1R) and circulating levels of corticosterone and leptin were also measured. Control males showed CPP after administration of MDMA. However, no MDMA-induced CPP was detected in control females or MD males, and MD had no effect on open field activity in any group. A reduction in striatal and cortical 5-HT levels, increased expression of hippocampal CB1R and a marked trend towards higher circulating leptin levels were observed in MDMA-treated MD males. Our results demonstrate for the first time that MD reduces the rewarding effects of MDMA in a sex-dependent manner. We propose that this effect is related, at least in part, with alterations of the serotonergic and cannabinoid systems. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Llorente-Berzal, Alvaro AU - Llorente-Berzal A AD - Depto. Fisiologia (Fisiologia Animal II), Fac Biologia, Universidad Complutense, Madrid, Spain. FAU - Manzanedo, Carmen AU - Manzanedo C FAU - Daza-Losada, Manuel AU - Daza-Losada M FAU - Valero, Manuel AU - Valero M FAU - Lopez-Gallardo, Meritxell AU - Lopez-Gallardo M FAU - Aguilar, Maria A AU - Aguilar MA FAU - Rodriguez-Arias, Marta AU - Rodriguez-Arias M FAU - Minarro, Jose AU - Minarro J FAU - Viveros, Maria-Paz AU - Viveros MP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121214 PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Aging/drug effects/physiology MH - Animals MH - Brain/*drug effects/metabolism MH - Brain Chemistry/*drug effects/physiology MH - Conditioning, Classical/*drug effects/physiology MH - Female MH - Male MH - *Maternal Deprivation MH - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity MH - Rats MH - Rats, Wistar MH - *Sex Characteristics OTO - NOTNLM OT - Adolescence OT - CB(1) receptor OT - Conditioned place preference OT - MDMA OT - Maternal deprivation OT - Serotonergic system EDAT- 2012/12/19 06:00 MHDA- 2013/10/26 06:00 CRDT- 2012/12/19 06:00 PHST- 2012/09/25 00:00 [received] PHST- 2012/12/04 00:00 [revised] PHST- 2012/12/05 00:00 [accepted] PHST- 2012/12/19 06:00 [entrez] PHST- 2012/12/19 06:00 [pubmed] PHST- 2013/10/26 06:00 [medline] AID - S0300-483X(12)00422-2 [pii] AID - 10.1016/j.tox.2012.12.003 [doi] PST - ppublish SO - Toxicology. 2013 Sep 6;311(1-2):78-86. doi: 10.1016/j.tox.2012.12.003. Epub 2012 Dec 14.