Sex-specific attenuation of impulsive action by progesterone in a go/no-go task for cocaine in rats

Previous work indicated that progesterone (PRO) reduced impulsive choice for cocaine in female but not male rats (Smethells et al. Psychopharmacology 233:2999-3008, 2016). Impulsive action, typically measured by responding for a reinforcer during a signaled period of nonavailability of natural reinforcers, predicts initiation and escalation of drug use in animals and humans. The present study examined impulsive action for cocaine using PRO in male and female rats trained on a go/no-go task. Rats were trained on a go/no-go task to respond for cocaine infusions (0.4 mg/kg/inf). During the "go" component, responding was reinforced on a VI 30-s schedule, whereas during the "no-go" component, withholding a response was reinforced on a differential reinforcement of other behavior (DRO) 30-s schedule. A response during the no-go component resets the DRO timer and served as a measure of impulsive action. After baseline responding was established, rats were pretreated with vehicle (VEH) or PRO (0.5 mg/kg), and DRO resets and responding during the go component for cocaine were compared in males vs. females. DRO resets were significantly lower following PRO treatment compared to VEH in female, but not male, rats. Response rates and overall infusions during the go component were not significantly altered by PRO in either females or males. Treatment with PRO resulted in a sex-specific reduction in impulsive action for cocaine, while not affecting cocaine self-administration.