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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Animals
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Behavior, Animal / drug effects*
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Cerebral Cortex / physiopathology
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Cognition / drug effects*
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Dronabinol / pharmacology*
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Exploratory Behavior / drug effects
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Female
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Gene Expression / drug effects
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Hallucinogens / pharmacology*
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Hippocampus / drug effects
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Hippocampus / metabolism
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Hippocampus / physiopathology
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Humans
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Hypothalamus / drug effects
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Hypothalamus / metabolism
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Hypothalamus / physiopathology
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Male
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Maze Learning / drug effects
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism
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N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neuropeptides / genetics
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Neuropeptides / metabolism
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Orexins
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Rats
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Rats, Wistar
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Sex Factors
Substances
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Cytoskeletal Proteins
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Hallucinogens
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Intracellular Signaling Peptides and Proteins
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Nerve Tissue Proteins
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Neuropeptides
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Orexins
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activity regulated cytoskeletal-associated protein
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Dronabinol
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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N-Methyl-3,4-methylenedioxyamphetamine
Grants and funding
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. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.