Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption

• Published in: PloS one 2013-11, Vol.8 (11), p.e78386
• Main Authors: Llorente-Berzal, Alvaro, Puighermanal, Emma, Burokas, Aurelijus, Ozaita, Andrés, Maldonado, Rafael, Marco, Eva M, Viveros, Maria-Paz
• Format: Article
• Language: English
• Subjects: Adolescent; Animal cognition; Animals; Anxiety; Behavior; Behavior, Animal - drug effects; Body temperature; Cannabis; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Child development; Cognition - drug effects; Cognitive ability; Cortex (frontal); Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Còrtex cerebral; Dopamine; Dronabinol - pharmacology; Drug abuse; Drug therapy; Ecstasy; Ecstasy (Drug); Exploratory Behavior - drug effects; Female; Females; Gender differences; Gene Expression - drug effects; Hallucinogens - pharmacology; Hipocamp (Cervell); Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - physiopathology; Humans; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Hypothalamus - physiopathology; Immunoreactivity; Inhibition; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Long-term effects; Male; Males; Marijuana; Maze Learning - drug effects; MDMA; Memory; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; mRNA; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system; Neuroendocrine system; Neuropeptides - genetics; Neuropeptides - metabolism; Orexins; Pharmacology; Protein expression; Proteins; Proteïna tirosina-quinasa; Psychology; Psychopharmacology; Rats; Rats, Wistar; Reduction; Resveratrol; Rodents; Sex; Sex differences; Sex Factors; Studies; Teenagers; Tetrahydrocannabinol; Young adults; Youth
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078386

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.