Document Detail

Sex difference in cell proliferation in developing rat amygdala mediated by endocannabinoids has implications for social behavior.
MedLine Citation:
PMID:  21059913     Owner:  NLM     Status:  MEDLINE    
The amygdala is a sexually dimorphic brain region critical for the regulation of social, cognitive, and emotional behaviors, but both the nature and the source of sex differences in the amygdala are largely unknown. We have identified a unique sex difference in the developing rat medial amygdala (MeA) that is regulated by cannabinoids. Newborn females had higher rates of cell proliferation than males. Treatment of neonates with the cannabinoid receptor agonist, WIN 55,212-2 (WIN), reduced cell proliferation in females to that of males and a wide range of WIN doses had no effect on cell proliferation in males. The effect of WIN on cell proliferation in the MeA was prevented by coinfusions of a CB2 but not CB1 receptor antagonist. Females had higher amygdala content of the endocannabinoid degradation enzymes, fatty acid amid hydrolase, and monoacylglycerol lipase than males, and lower amounts of the endocannabinoids 2-arachidonoylglycerol and N-arachidonylethanolamide (anandamide). Inhibition of the degradation of 2-arachidonoylglycerol in females occluded the sex difference in cell proliferation. Analyses of cell fate revealed that females had significantly more newly generated glial cells but not more newly generated neurons than males, and treatment with WIN significantly decreased glial cell genesis in females but not males. Finally, early exposure to cannabinoids masculinized juvenile play behavior in females but did not alter this behavior in males. Collectively, our findings suggest that sex differences in endocannabinoids mediate a sex difference in glial cell genesis in the developing MeA that impacts sex-specific behaviors in adolescence.
Desiree L Krebs-Kraft; Matthew N Hill; Cecilia J Hillard; Margaret M McCarthy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-01-20     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  20535-40     Citation Subset:  IM    
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
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MeSH Terms
Amidohydrolases / metabolism
Amygdala / cytology,  growth & development*
Analysis of Variance
Animals, Newborn
Benzoxazines / pharmacology
Blotting, Western
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators / metabolism*
Cell Proliferation / drug effects*
Fluorescent Antibody Technique
Microscopy, Confocal
Monoacylglycerol Lipases / metabolism
Morpholines / pharmacology
Naphthalenes / pharmacology
Neurogenesis / drug effects*
Neuroglia / drug effects*
Sex Characteristics*
Social Behavior*
Grant Support
R01 MH052716/MH/NIMH NIH HHS; R21 DA022439/DA/NIDA NIH HHS; T32 NS07375/NS/NINDS NIH HHS; //Canadian Institutes of Health Research
Reg. No./Substance:
0/Benzoxazines; 0/Cannabinoid Receptor Agonists; 0/Cannabinoid Receptor Modulators; 0/Endocannabinoids; 0/Morpholines; 0/Naphthalenes; 134959-51-6/Win 55212-2; EC Lipases; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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