Analyzing the Effects of Gonadal Hormones on Alcohol Seeking and Drinking in Alcohol-Preferring P Rats

Abstract

Female and male rodents have shown differences in alcohol-seeking and -drinking behaviors, with female rodents typically consuming more alcohol than male rodents. Differences in gonadal hormones may provide one explanation for these sex differences. The current study used selectively bred female and male alcohol-preferring (P) rats to assess sex differences and the possible impacts of circulating gonadal hormones on alcohol seeking and drinking in an operant appetitive/consummatory paradigm. P rats were trained in operant boxes first for water and then 20% alcohol. Rats then underwent ovariectomy (OVX), castration (CAST), or sham surgeries. After recovery from surgery, rats that underwent OVX or CAST surgery then started receiving daily subcutaneous (s.c.) injections of either estradiol benzoate (E2), testosterone (T), or vehicle (Veh) which began five days prior to additional operant testing and lasted throughout the study. Rats were given a response requirement (RR) Monday-Thursday where they had 20-minutes to meet the required lever presses which resulted in 20-minute access to alcohol. Testing occurred over three weeks which resulted in 12 days of alcohol-drinking behavior. On Fridays, rats were given a 20-minute extinction session where number of lever presses were recorded which resulted in three days of alcohol-seeking behavior. Overall, females drank more alcohol than males in both training and testing. This was seen in both Veh and Sham rats. There were no sex differences in alcohol-seeking behavior. There was no effect of E2 or T in either sex as there were no differences in alcohol intake or lever presses during extinction compared to Veh groups. There were also no sex or group differences in blood ethanol concentrations (BEC), but BEC did correlate with alcohol intake. This study is one of the first examining gonadal hormones in a selectively bred line of rat that prefers to drink alcohol and is unique in that it included both females and males in each of the treatment groups. The activational effects of gonadal hormones may have a limited impact on alcohol-related behaviors in P rats, but more research is needed to make definitive conclusions about their role.