Despite the prevalence of cocaine addiction among women, few investigators have included females as subjects in cocaine self-administration experiments. Recent reports indicate gender differences in all phases of the addiction process including initiation and prevalence of use, patterns and levels of use, the progression to addiction, withdrawal, and relapse. While similar sex differences have also been observed in animals, few studies have investigated sex differences during the transition to addiction or the mechanisms that may underlie sex differences.
Specific Aim 1 will characterize sex differences in cocaine self-administration behavior using a 24-hr access procedure that leads to high levels of intake and dysregulated patterns of use, features that may reflect compulsive aspects of addiction. An additional goal of Aim 1 is to explore the molecular and hormonal mechanisms that may underlie sex differences under high cocaine access conditions.
Aim 2 will characterize the effects of high access to cocaine on subsequent motivational and behavioral changes and how these changes may differ by sex and ovarian hormone status. Specifically, we will investigate motivation to obtain cocaine as measured by responding under the progressive ratio schedule during early withdrawal (i.e., 0-72 hr) and after an extended drug-free period (i.e., 10-days). Additionally, since previous work has shown that chronic cocaine exposure produces not only motivational changes but is also associated with deficits in impulse control, Aim 3 will investigate the effects of high cocaine access on measures of impulsivity using a delay-discounting task. These experiments are of significance for drug abuse research and women's health research since they may help to identify molecular adaptations that occur following chronic cocaine self-administration and hormonal mechanisms that may underlie sex differences in vulnerability to cocaine addiction. Thus, these studies may provide a basis for the development of novel treatment strategies for cocaine abuse/dependence, particularly in women.
