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Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption.
PLoS One 2013; 8(11):e78386Plos

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.

Authors+Show Affiliations

Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain ; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24223797

Citation

Llorente-Berzal, Alvaro, et al. "Sex-dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption." PloS One, vol. 8, no. 11, 2013, pp. e78386.
Llorente-Berzal A, Puighermanal E, Burokas A, et al. Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption. PLoS ONE. 2013;8(11):e78386.
Llorente-Berzal, A., Puighermanal, E., Burokas, A., Ozaita, A., Maldonado, R., Marco, E. M., & Viveros, M. P. (2013). Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption. PloS One, 8(11), pp. e78386. doi:10.1371/journal.pone.0078386.
Llorente-Berzal A, et al. Sex-dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption. PLoS ONE. 2013;8(11):e78386. PubMed PMID: 24223797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption. AU - Llorente-Berzal,Alvaro, AU - Puighermanal,Emma, AU - Burokas,Aurelijus, AU - Ozaita,Andrés, AU - Maldonado,Rafael, AU - Marco,Eva M, AU - Viveros,Maria-Paz, Y1 - 2013/11/04/ PY - 2013/07/02/received PY - 2013/09/18/accepted PY - 2013/11/14/entrez PY - 2013/11/14/pubmed PY - 2014/8/13/medline SP - e78386 EP - e78386 JF - PloS one JO - PLoS ONE VL - 8 IS - 11 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24223797/Sex_dependent_psychoneuroendocrine_effects_of_THC_and_MDMA_in_an_animal_model_of_adolescent_drug_consumption_ L2 - http://dx.plos.org/10.1371/journal.pone.0078386 DB - PRIME DP - Unbound Medicine ER -