Animals can easily develop new food preferences and aversions through associative learning. If they consume a novel flavor and experience malaise, they develop an aversion towards that particular flavor, food or fluid. Conditioned taste aversion (CTA) requires gene expression and histone acetylation, which can be enhanced by HDAC inhibitors such as sodium butyrate (NaB). Here, I sought to determine whether enhancement of CTA using NaB is subject to sex-specific differences through changes in histone modification. Adult male (n=32) and female (n=32) Sprague-Dawley rats were placed on water restriction for 7 days with ad lib food to ensure intake on conditioning day. On the conditioning day, they were given 30 min access to saccharin (0.125%) and then injected with either sodium chloride (NaCl) or lithium chloride (LiCl; 0.15M, 3ml/kg). Ten minutes later, half the rats were injected with NaB (0.3M, 12ml/kg) or NaCl (0.3M, 12ml/kg. Thus, there were 4 groups for each sex: NaCl-NaCl, NaCl-NaB, LiCl-NaCl, and LiCl-NaB. Beginning the next day, 2-bottle 24-h preference tests of water vs. saccharin was carried out for 10 days. NaCl-NaCl and NaCl-NaB groups showed high preference for saccharin throughout 2-bottle testing. Male LiCl-NaCl showed moderate CTA which extinguished over the 10 days of preference testing. Male rats injected with LiCl-NaB appeared to have a greater CTA than LiCl-NaCl rats. However, NaB did not appear to enhance CTA in the LiCl-NaB-injected females compared to LiCl-NaCl injected rats. Thus, female rats appear to be less sensitive to the CTA-potentiated effects of NaB. I wanted to check if the effect of NaB is generalizable and if there is a hormonal influence in female rats blunting the NaB-mediated conditioned taste aversion. Therefore, I used another HDAC inhibitor sodium valproate (Val) to see if I get similar results. For this experiment, I used adult male (n=20) and female (n=20) rats and found that at 100mg/kg of Val, similar to observations with NaB, LiCl-induced CTA was enhanced in male rats but not in female rats. Next, I wanted to test the role of estrogen in female rats. For this experiment I used 36 adult female rats. I divided them into three groups where the first group of rats were ovariectomized, the second group were ovariectomized with estradiol pellet implant, and the third group had a sham surgery with intact ovaries. I found that CTA was not enhanced in ovariectomized with estrogen pellet group. Finally, I assessed if the sex differences were due to a difference in basal HDAC activity between males and females, by using adult male (n=4) and female (n=4) rats and found that the males had a higher HDAC activity in brainstem and amygdala than females and also female rats are less sensitive to HDAC inhibitors.
