PMID- 24223797
OWN - NLM
STAT- MEDLINE
DCOM- 20140808
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of 
      adolescent drug consumption.
PG  - e78386
LID - 10.1371/journal.pone.0078386 [doi]
LID - e78386
AB  - 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.
FAU - Llorente-Berzal, Alvaro
AU  - Llorente-Berzal A
AD  - Departamento de Fisiologia (Fisiologia Animal II), Facultad de Biologia, 
      Universidad Complutense de Madrid, Madrid, Spain ; Instituto de Investigacion 
      Sanitaria del Hospital Clinico San Carlos, Madrid, Spain.
FAU - Puighermanal, Emma
AU  - Puighermanal E
FAU - Burokas, Aurelijus
AU  - Burokas A
FAU - Ozaita, Andres
AU  - Ozaita A
FAU - Maldonado, Rafael
AU  - Maldonado R
FAU - Marco, Eva M
AU  - Marco EM
FAU - Viveros, Maria-Paz
AU  - Viveros MP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131104
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Hallucinogens)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Orexins)
RN  - 0 (activity regulated cytoskeletal-associated protein)
RN  - 7J8897W37S (Dronabinol)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
EIN - PLoS One. 2013;8(12). doi:10.1371/annotation/89e38eb6-e8e3-402d-a6fb-84ebf9fcbb27
MH  - Adolescent
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Cerebral Cortex/drug effects/metabolism/physiopathology
MH  - Cognition/*drug effects
MH  - Cytoskeletal Proteins/genetics/metabolism
MH  - Dronabinol/*pharmacology
MH  - Exploratory Behavior/drug effects
MH  - Female
MH  - Gene Expression/drug effects
MH  - Hallucinogens/*pharmacology
MH  - Hippocampus/drug effects/metabolism/physiopathology
MH  - Humans
MH  - Hypothalamus/drug effects/metabolism/physiopathology
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Male
MH  - Maze Learning/drug effects
MH  - Mitogen-Activated Protein Kinase 1/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/genetics/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neuropeptides/genetics/metabolism
MH  - Orexins
MH  - Rats
MH  - Rats, Wistar
MH  - Sex Factors
PMC - PMC3817254
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/14 06:00
MHDA- 2014/08/13 06:00
PMCR- 2013/11/04
CRDT- 2013/11/14 06:00
PHST- 2013/07/02 00:00 [received]
PHST- 2013/09/18 00:00 [accepted]
PHST- 2013/11/14 06:00 [entrez]
PHST- 2013/11/14 06:00 [pubmed]
PHST- 2014/08/13 06:00 [medline]
PHST- 2013/11/04 00:00 [pmc-release]
AID - PONE-D-13-27080 [pii]
AID - 10.1371/journal.pone.0078386 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 4;8(11):e78386. doi: 10.1371/journal.pone.0078386. eCollection 
      2013.