Influence of Gonadal Hormones on Motivation for a Sucrose Reward in Female Rats: Alterations following Exposure to Haloperidol and Apomorphine

Abstract

IntroductionSex differences in dysfunction of motivational systems for natural rewards has been implicated in several disorders, including depression, obesity, and substance abuse (Pulcu & Elliott, 2015; Volkow & Wise, 2005). Sex differences are evident in these motivational disorders, and our lab has previously shown that female rats work harder for a natural sucrose reward compared to male rats. Interestingly, dopamine regulates motivated behaviors and may be important for understanding these sex differences in motivation. Previous research has found that haloperidol and apomorphine decrease responding for sucrose rewards, and gonadal hormones may influence sensitivity to these dopaminergic alterations. Although the role of gonadal hormones on motivation for drug rewards such as cocaine has been studied, little research has measured motivation for a natural sucrose reward following hormone manipulation. Further, it is not known if gonadal hormones alter sensitivity to haloperidol and apomorphine, as measured by responding for a sucrose reward. Therefore, the current study investigated the role estrogen and progesterone had on motivation for a sucrose reward and how these hormones alter sensitivity to dopaminergic manipulations (i.e. haloperidol and apomorphine injections).MethodsSeventy adult female rats were randomly assigned to one of five experimental groups: intact, ovariectomized (ovx) that received vehicle, ovx that received estradiol benzoate, ovx that received progesterone, or ovx that received both estradiol benzoate and progesterone. All rats were trained to lever press on an autoshaping schedule followed by an increasing fixed ratio schedule (FR1, FR3, FR5). Rats were then given three progressive ratio (PR) tests to assess motivation following gonadal hormone manipulation, a .032 mg/kg haloperidol injection, or a .032 mg/kg apomorphine injection. Throughout training and testing, hormones were administered every four to five days to mimic the endogenous estrous cycle. Estradiol benzoate was administered 48 hours and progesterone administered 4 hours prior to each PR test.ResultsNeither ovx nor hormone restoration altered the number of active lever presses, suggesting similar motivational responding across all groups. The dopamine antagonist haloperidol decreased active lever responding overall compared to PR responding without drug, but hormone condition did not influence this change. The dopamine agonist apomorphine differentially altered responding, depending on the hormone condition. Ovx females receiving estradiol with progesterone had significantly greater active lever responding compared to ovx females receiving vehicle following apomorphine. However, neither estradiol benzoate nor progesterone treated females differed from ovx with vehicle.DiscussionGonadal hormones do not seem to influence motivation for a sucrose reward in female rats or responding following haloperidol exposure. However, gonadal hormones alter behavioral sensitivity to apomorphine. These findings suggest gonadal hormones may contribute to altered sensitivity to dopaminergic manipulations, which has implications for disorders such as depression, obesity, and substance abuse.