[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 278.9/MM2
Topic: E.01.d. Development
Support: NIH Grant RO1 MH052716
NIH Grant T32 NS07375
Title: The cannabinoid agonist, WIN 55,212-2, decreases the number of new cells that express
GFAP in the developing medial amygdala of female rats
Authors: *D. L. KREBS-KRAFT, M. M. MCCARTHY;
Dept of Physio, Program in Neurosci., Univ. of Maryland Baltimore, Sch. of Med., Baltimore,
MD
Abstract: The amygdala is an important brain region in the regulation of social, cognitive, and
emotional behaviors. There are volumetric sex differences in the medial amygdala of
peripubertal and adult rats, such that the regional volume of the medial amygdala is larger in
males than females (Cooke, 2007; Mizukami et al, 1983). In most brain regions, volumetric sex
differences are attributed to higher rates of cell death in one sex versus the other; however, cell
proliferation may also be important. Cannabinoids are developmentally regulated retrograde
messengers that have been implicated in brain development and can modulate cell proliferation
and differentiation of neural cell types (Aguado et al, 2005, 2006; Galve-Roperh et al, 2006).
There are sex differences in cannabinoid effects on behavior in adults, such that females are
more susceptible to the effects of cannabinoid activation. We find females have more new cells,
detected by 5-bromo-2‟-deoxyuridine-5‟-monophosphate (BrdU), in the developing amygdala
than males. Treatment of neonates with a cannabinoid receptor agonist, WIN 55,212-2 (WIN),
reduces the number of new cells in females to that of males. Astrocytes play a critical role in
neurotransmission, axon guidance, and synapse formation and cannabinoids modulate glial
differentiation (Aguado et al, 2006). The present study tested the hypothesis that cannabinoids
modulate glial cell proliferation or survival in the developing medial amygdala of females. The
number of newly generated glial cells was detected by double-label immunohistochemistry using
a monoclonal antibody specific for BrdU, a marker of cell genesis, and glial fibrillary acidic
protein (GFAP), a maker for mature astrocytes. Specifically, we determined whether treating
males and females at postnatal day 0 and 1 with WIN (1 mg/kg) would decrease the number of
BrdU, GFAP, and BrdU/GFAP immunoreactive cells in the rat medial amygdala at postnatal day
4 or 14, in comparison to vehicle treated controls. Consistent with our previous findings, females
had significantly more BrdU+ and BrdU+/GFAP+ cells in the medial amygdala than did males at
PN4 and PN14. More importantly, treatment with WIN significantly decreased the number of
BrdU+ and BrdU+/GFAP+ cells in females but not males. These findings suggest that
cannabinoids modulate glial cell proliferation, survival, and/or differentiation in the developing
medial amygdala.
Disclosures: D.L. Krebs-Kraft , None; M.M. McCarthy, None.