PMID- 24236988
OWN - NLM
STAT- MEDLINE
DCOM- 20141105
LR  - 20240520
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 171
IP  - 6
DP  - 2014 Mar
TI  - Sex-dependent long-term effects of adolescent exposure to THC and/or MDMA on 
      neuroinflammation and serotoninergic and cannabinoid systems in rats.
PG  - 1435-47
LID - 10.1111/bph.12519 [doi]
AB  - BACKGROUND AND PURPOSE: Many young people consume ecstasy as a recreational drug 
      and often in combination with cannabis. In this study, we aimed to mimic human 
      consumption patterns and investigated, in male and female animals, the long-term 
      effects of Delta(9) -tetrahydrocannabinol (THC) and 3,4-methylenedioxymethamphetamine 
      (MDMA) on diverse neuroinflammation and neurotoxic markers. EXPERIMENTAL 
      APPROACH: Male and female Wistar rats were chronically treated with increasing 
      doses of THC and/or MDMA during adolescence. The effects of THC and/or MDMA on 
      glial reactivity and on serotoninergic and cannabinoid systems were assessed by 
      immunohistochemistry in the hippocampus and parietal cortex. KEY RESULTS: THC 
      increased the area staining for glial fibrilar acidic protein in both sexes. In 
      males, both drugs, either separately or in combination, increased the proportion 
      of reactive microglia cells [ionized calcium binding adaptor molecule 1 (Iba-1)]. 
      In contrast, in females, each drug, administered alone, decreased of this 
      proportion, whereas the combination of both drugs resulted in a 'normalization' 
      to control values. In males, MDMA reduced the number of SERT positive fibres, THC 
      induced the opposite effect and the group receiving both drugs did not 
      significantly differ from the controls. In females, MDMA reduced the number of 
      SERT positive fibres and the combination of both drugs counteracted this effect. 
      THC also reduced immunostaining for CB1 receptors in females and this effect was 
      aggravated by the combination with MDMA. CONCLUSIONS AND IMPLICATIONS: Adolescent 
      exposure of rats to THC and/or MDMA induced long-term, sex-dependent 
      neurochemical and glial alterations, and revealed interactions between the two 
      drugs. LINKED ARTICLES: This article is part of a themed section on Cannabinoids 
      2013. To view the other articles in this section visit 
      http://dx.doi.org/10.1111/bph.2014.171.issue-6.
CI  - (c) 2013 The British Pharmacological Society.
FAU - Lopez-Rodriguez, Ana Belen
AU  - Lopez-Rodriguez AB
AD  - Department of Animal Physiology (Animal Physiology II), Faculty of Biology, 
      Complutense University of Madrid - Instituto de Investigacion Sanitaria del 
      Hospital Clinico San Carlos (IdISSC), Madrid, Spain; Instituto Cajal, Consejo 
      Superior de Investigaciones Cientificas (CSIC), Madrid, Spain.
FAU - Llorente-Berzal, Alvaro
AU  - Llorente-Berzal A
FAU - Garcia-Segura, Luis M
AU  - Garcia-Segura LM
FAU - Viveros, Maria-Paz
AU  - Viveros MP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Aif1 protein, rat)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Cannabinoids)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 333DO1RDJY (Serotonin)
RN  - 7J8897W37S (Dronabinol)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adolescent
MH  - Animals
MH  - Calcium-Binding Proteins/metabolism
MH  - Cannabinoids/*metabolism
MH  - Dronabinol/*pharmacology
MH  - Encephalitis/metabolism/*physiopathology
MH  - Female
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Humans
MH  - Male
MH  - Microfilament Proteins/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Cannabinoid, CB1/metabolism
MH  - Serotonin/*metabolism
MH  - *Sex Factors
PMC - PMC3954483
OTO - NOTNLM
OT  - CB1 receptor
OT  - MDMA
OT  - THC
OT  - adolescence
OT  - astrocytes
OT  - reactive microglia
OT  - serotonin transporter
OT  - sex differences
EDAT- 2013/11/19 06:00
MHDA- 2014/11/06 06:00
PMCR- 2015/03/01
CRDT- 2013/11/19 06:00
PHST- 2013/05/31 00:00 [received]
PHST- 2013/11/07 00:00 [revised]
PHST- 2013/11/13 00:00 [accepted]
PHST- 2013/11/19 06:00 [entrez]
PHST- 2013/11/19 06:00 [pubmed]
PHST- 2014/11/06 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - 10.1111/bph.12519 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2014 Mar;171(6):1435-47. doi: 10.1111/bph.12519.