Sex difference in cell proliferation in developing rat amygdala mediated by endocannabinoids has implications for social behavior. Proc Natl Acad Sci U S A 2010 Nov 23;107(47):20535-40
Date
11/10/2010Pubmed ID
21059913Pubmed Central ID
PMC2996668DOI
10.1073/pnas.1005003107Scopus ID
2-s2.0-78650553198 (requires institutional sign-in at Scopus site) 96 CitationsAbstract
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.
Author List
Krebs-Kraft DL, Hill MN, Hillard CJ, McCarthy MMAuthor
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AmidohydrolasesAmygdala
Analysis of Variance
Animals
Animals, Newborn
Benzoxazines
Blotting, Western
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Cell Proliferation
Endocannabinoids
Female
Fluorescent Antibody Technique
Immunohistochemistry
Male
Microscopy, Confocal
Monoacylglycerol Lipases
Morpholines
Naphthalenes
Neurogenesis
Neuroglia
Rats
Sex Characteristics
Social Behavior
