Llorente Berzal, AlvaroPuighermanal Puigvert, Emma, 1983-Burokas, Aurelijus, 1982-Ozaita Mintegui, Andrés, 1969-Maldonado, Rafael, 1961-Viveros, Maria Paz2015-05-212015-05-212013Llorente-Berzal A, Puighermanal E, Burokas A, Ozaita A, Maldonado R, Marco EM, Viveros MP. Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption. PLoS ONE. 2013;8(11):e78386. DOI: 10.1371/journal.pone.00783861932-6203http://hdl.handle.net/10230/23606Ecstasy 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.application/pdfeng© 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 creditedCòrtex cerebralHipocamp (Cervell)Proteïna tirosina-quinasainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1371/journal.pone.0078386info:eu-repo/semantics/openAccess