|
Title:
|
Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption
|
|
Author:
|
Llorente Berzal, Alvaro; Puighermanal Puigvert, Emma, 1983-; Burokas, Aurelijus, 1982-; Ozaita Mintegui, Andrés, 1969-; Maldonado, Rafael, 1961-; Viveros, Maria Paz
|
|
Abstract:
|
Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46), MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB), whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs. |
|
Abstract:
|
Instituto de Salud Carlos III, Redes temáticas de Investigación Cooperativa en salud (ISCIII y FEDER): Red de trastornos adictivos RD06/0001/1013,RD2012/0028/0021 and RD06/001/001; GRUPOS UCM-BSCH (GRUPO UCM 951579); Plan Nacional sobre Drogas en la convocatoria de Orden SAS/1250/2009. ALB has a FPU predoctoral grant from the Ministerio de Ciencia e Innovación. |
|
Subject(s):
|
-Còrtex cerebral
-Hipocamp (Cervell)
-Proteïna tirosina-quinasa |
|
Rights:
|
© 2013 Llorente-Berzal et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
|
|
Document type:
|
Article
Article - Published version |
|
Published by:
|
Public Library of Science (PLoS)
|
|
Share:
|
|
