Abstract
We showed an effect of supraphysiological levels of E2 (10μg/14 days) on components of the CREB signaling pathway, including pCREB protein levels, in the MeA of OVX rats. To determine if physiological doses of E2 affect pCREB-immunoperoxidase-positive nuclear number and volume in the MeA, we injected OVX rats with 2.5μg E2 for 4 (2.5/4) or 14 (2.5/14) days or 10μg E2 for 14 days (10/14); sesame oil (SO) was the control (N=4 per group). Both 2.5μg treatments resulted in physiological blood E2 levels, but 10/14 resulted in levels that were 3X higher. Using StereoInvesigator (MicroBrightfield) software, we found a significant increase in number of pCREB-positive nuclei in left whole MeA in 10/14 compared to 2.5/4 (p<0.01) and SO (p<0.05), and in 2.5/14 compared to 2.5/4 (p<0.01) and SO (p<0.05); no differences were seen between 10/14 and 2.5/14 or between 2.5/4 and SO. There was a trend toward increase in volume of whole left MeA between 10/14 and SO and between 2.5/14 and SO. There was a trend toward increased number of pCREB-positive nuclei in the left posterior dorsal + posterior ventral (LP) MeA in 10/14 and 2.5/14 vs 2.5/4. There was also a trend toward increased volume of LPMeA between 10/14 and 2.5/4. No differences in any of the parameters were seen in the central amygdala among any of the groups. Physiological doses of E2 for 14 days, but not 4 days, appear to significantly affect pCREB-positive nuclear number in the left whole MeA. Supported by NIH grant MH065990.
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