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

Abstract

Rationale Previous work indicated that progesterone (PRO) reduced impulsive choice for cocaine in female but not male rats (Smethells et al. 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 progesterone (PRO) in male and female rats trained on a Go/No-go task. Objective 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 reset 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. Results 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. Conclusion Treatment with PRO resulted in a sex-specific reduction in impulsive action for cocaine, while not affecting cocaine self-administration.

Influence of ovarian hormones on value-based decision-making systems: Contribution to sexual dimorphisms in mental disorders

“…Conversely, the 'No-Go' response for cocaine in a temporal delay task was stronger in female but not male rats when treated with both unopposed progesterone and in combination with atomoxetine, a selective noradrenaline reuptake inhibitor (Smethells et al, 2016). Similarly, progesterone treatment affected female but not male rats in reducing impulsive 'Go' responses to cocaine when 'No-Go' was required, yet no effect of progesterone treatment was found for cocaine self-administration (Swalve et al, 2018). The findings are consistent with effects of varying endogenous levels of progesterone in female rats: cocaine seeking is lowest in a high progesterone state and highest in the low progesterone state (Feltenstein and See, 2007).…”

“…Taken together, these results indicate that progesterone differentially reduced impulsive action and impulsive choice for cocaine in female rats but less so in male rats. It was suggested that a potential mechanism of progesterone's actions on drug use might be its ability to reduce impulsive drug seeking (Swalve et al, 2018). Notably, effects of estradiol in temporal delay tasks, however, have not been investigated in rodents.…”

Brain and Cognition for Addiction Medicine: From Prevention to Recovery Neural Substrates for Treatment of Psychostimulant-Induced Cognitive Deficits

“…The hypocretin/orexin system plays an important role in the reinforcing effects of cocaine. For example, suvorexant, a dual orexin receptor antagonist, attenuated both the rewarding and motivational effects of cocaine (141). Also, knockdown of hypocretin/orexin neurons in the dorsal hypothalamus attenuated cocaine self-administration (246).…”

“…Treatment with progesterone attenuated decisional impulsivity for food reward in both males and females (375). Interestingly, progesterone alone attenuated both behavioral and decisional impulsivity for cocaine rewards in female but not male rats (141, 142) ( Table 2 ). These data suggest that sex gonadal hormones influence impulsive behaviors.…”

Association of exercise with smoking-related symptomatology, smoking behavior and impulsivity in men and women

“…Another key factor related to smoking cessation and relapse is impulsivity (a multidimensional trait comprised of attentional, motor and non-planning factors), which has been discussed and reviewed in recent studies (Balevich et al, 2013;Carroll et al, 2009;Carroll and Holtz, 2014;Carroll and Smethells, 2016;Flory and Manuck, 2009;Mitchell, 1999;Perry and Carroll, 2008;Reynolds et al, 2004;Smethells et al, 2016;Swalve et al, 2017). Recent studies have shown that the non-planning facet is specifically associated with poorer response to smoking cessation treatments (López-Torrecillas et al, 2014) and impulsivity/disinhibition may predict successful smoking cessation through treatment (Stevens et al, 2014).…”