The Effects of Estradiol on Cocaine Intake in Female HR and LR Rats

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DESCRIPTION (provided by applicant): Sex differences and individual differences influence the development of substance use disorders. For example, a greater number of men are addicted to cocaine, yet women get addicted to cocaine at earlier ages and demonstrate a greater dependence for cocaine than men. Similarly, female rats acquire cocaine self-administration more rapidly than males and will self-administer more cocaine than males. These sex differences are at least in part due to estradiol. When estradiol is high in female rats, they will self-administer more cocaine than when estradiol levels are low. In addition to sex differences and the effects of estradiol, individual differences influence cocaine addiction in humans and rats. Persons with the individual personality trait for novelty seeking are more likely to try drugs and, therefore, develop addictions. Rats that show high locomotor behavior in response to a novel environment (high responders, HR) show similar tendencies to human novelty seekers in that they will acquire self-administration behavior for cocaine more rapidly than rats that show a low locomotor behavioral response to a novel environment (low responders, LR). Therefore, rats with the HR phenotype are used as a model for human novelty seekers. My studies use rats that have been selectively-bred for the HR and LR phenotypes. My data demonstrate that selectively-bred HR males and females will acquire cocaine self-administration more rapidly than LR males and females. In addition, female HR rats take more cocaine than HR males, LR males and LR females. Using this same line of rats, I intend to test for the effects of estradiol and phenotype differences on cocaine self-administration in female HR and LR rats in order to determine what part estradiol plays in the afore mentioned differences. The specific aims of this proposal include: Specific Aim 1, which will determine how estradiol and the HR and LR phenotypes interact to influence on acquisition of cocaine self-administration in female rats; Specific Aim 2, which will determine how estradiol and the HR and LR phenotypes impact motivation to take cocaine in female rats; and Specific Aim 3 will determine how estradiol and the HR or LR phenotypes influence reinstatement of cocaine self-administration behavior in female rats. To investigate these aims I will be using female rats that are selectively-bred for the HR or LR phenotype. PUBLIC HEALTH RELEVANCE: My main objective for this proposal is to better understand how hormones (e.g. estradiol) and individual personality traits influence substance use disorders in females. This is crucial for the treatment of substance use disorders in women and for the development of programs for the prevention of such disorders, which is crucial to improving public health.