PMID- 31193575
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 2352-2895 (Print)
IS  - 2352-2895 (Electronic)
IS  - 2352-2895 (Linking)
VI  - 10
DP  - 2019 Feb
TI  - Noradrenergic depletion causes sex specific alterations in the endocannabinoid 
      system in the Murine prefrontal cortex.
PG  - 100164
LID - 10.1016/j.ynstr.2019.100164 [doi]
LID - 100164
AB  - Brain endocannabinoids (eCB), acting primarily via the cannabinoid type 1 
      receptor (CB1r), are involved in the regulation of many physiological processes, 
      including behavioral responses to stress. A significant neural target of eCB 
      action is the stress-responsive norepinephrine (NE) system, whose dysregulation 
      is implicated in myriad psychiatric and neurodegenerative disorders. Using 
      Western blot analysis, the protein expression levels of a key enzyme in the 
      biosynthesis of the eCB 2-arachidonoylglycerol (2-AG), diacylglycerol lipase-alpha 
      (DGL-alpha), and two eCB degrading enzymes monoacylglycerol lipase (MGL) and fatty 
      acid amide hydrolase (FAAH) were examined in a mouse model that lacks the 
      NE-synthesizing enzyme, dopamine beta-hydroxylase (DbetaH-knockout, KO) and in rats 
      treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4). 
      In the prefrontal cortex (PFC), DGL-alpha protein expression was significantly 
      increased in male and female DbetaH-KO mice (P < 0.05) compared to wild-type (WT) 
      mice. DbetaH-KO male mice showed significant decreases in FAAH protein expression 
      compared to WT male mice. Consistent with the DbetaH-KO results, DGL-alpha protein 
      expression was significantly increased in male DSP-4-treated rats (P < 0.05) when 
      compared to saline-treated controls. MGL and FAAH protein expression levels were 
      significantly increased in male DSP-4 treated rats compared to male saline 
      controls. Finally, we investigated the anatomical distribution of MGL and FAAH in 
      the NE containing axon terminals of the PFC using immunoelectron microscopy. MGL 
      was predominantly within presynaptic terminals while FAAH was localized to 
      postsynaptic sites. These results suggest that the eCB system may be more 
      responsive in males than females under conditions of NE perturbation, thus having 
      potential implications for sex-specific treatment strategies of stress-related 
      psychiatric disorders.
FAU - Urquhart, M A
AU  - Urquhart MA
AD  - Department of Pharmacology and Physiology, College of Medicine, Drexel 
      University, Philadelphia, PA, 19102, USA.
FAU - Ross, J A
AU  - Ross JA
AD  - Department of Pharmacology and Physiology, College of Medicine, Drexel 
      University, Philadelphia, PA, 19102, USA.
FAU - Reyes, B A S
AU  - Reyes BAS
AD  - Department of Pharmacology and Physiology, College of Medicine, Drexel 
      University, Philadelphia, PA, 19102, USA.
FAU - Nitikman, M
AU  - Nitikman M
AD  - Department of Pharmacology and Physiology, College of Medicine, Drexel 
      University, Philadelphia, PA, 19102, USA.
FAU - Thomas, S A
AU  - Thomas SA
AD  - Department of Systems Pharmacology and Translational Therapeutics, Perelman 
      School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
FAU - Mackie, K
AU  - Mackie K
AD  - Department of Psychological and Brain Sciences, Indiana University, Bloomington, 
      IN, 47405-2204, USA.
FAU - Van Bockstaele, E J
AU  - Van Bockstaele EJ
AD  - Department of Pharmacology and Physiology, College of Medicine, Drexel 
      University, Philadelphia, PA, 19102, USA.
LA  - eng
GR  - R01 DA020129/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20190410
PL  - United States
TA  - Neurobiol Stress
JT  - Neurobiology of stress
JID - 101643409
PMC - PMC6535650
EDAT- 2019/06/14 06:00
MHDA- 2019/06/14 06:01
PMCR- 2019/04/10
CRDT- 2019/06/14 06:00
PHST- 2019/01/03 00:00 [received]
PHST- 2019/03/01 00:00 [revised]
PHST- 2019/04/06 00:00 [accepted]
PHST- 2019/06/14 06:00 [entrez]
PHST- 2019/06/14 06:00 [pubmed]
PHST- 2019/06/14 06:01 [medline]
PHST- 2019/04/10 00:00 [pmc-release]
AID - S2352-2895(19)30001-3 [pii]
AID - 100164 [pii]
AID - 10.1016/j.ynstr.2019.100164 [doi]
PST - epublish
SO  - Neurobiol Stress. 2019 Apr 10;10:100164. doi: 10.1016/j.ynstr.2019.100164. 
      eCollection 2019 Feb.