Sex differences in response to amphetamine in adult Long–Evans rats performing a delay-discounting task

Abstract

The use of animal models to investigate experimental questions about impulsive behavior can provide valuable insight into problems that affect human health. The delay-discounting paradigm involves subjects choosing between smaller reinforcers delivered immediately and larger reinforcers that are delivered after a delay. This is an important experimental paradigm for examining impulsive choice in both laboratory species and humans. However, a shortcoming of previously published delay-discounting studies in animals is that typically only males were studied, reducing the applicability of these studies to human populations. In the present study, both female and male adult Long-Evans rats were trained to perform a delay-discounting task, with delays of 0, 5, 10, 20 and 40 s before delivery of the larger reinforcer. Because dopaminergic signaling is important in mediating this task, the effects of d-amphetamine and the dopamine receptor antagonist, cis-flupenthixol, on task performance were then examined. The main experimental measure was percent larger-reinforcer choice, which was defined as the percentage of experimental trials at each delay in which the delayed, larger reinforcer was chosen. There was not a sex difference in percent larger-reinforcer choice during baseline performance of the task. However, d-amphetamine administration disrupted choice in females, as evidenced by < 80% larger-reinforcer choice in half of the females, but none of the males, at 0.5 mg/kg. d-Amphetamine also differentially altered the latency to choose between immediate versus delayed reinforcers in females compared to males. In contrast, cis-flupenthixol did not have a sex-related effect on percent larger-reinforcer choice. These findings parallel the sex differences in response to amphetamine seen in human delay-discounting studies and underscore the importance of evaluating sex-based differences in baseline performance and in response to pharmacologic agents when utilizing animal models.

Sex differences and hormonal modulation of ethanol-enhanced risk taking in rats

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Sex differences in animal models of decision making

“…Within some of the rodent studies, however, there were more nuanced behavioral differences between males and females, suggesting that there may be subtle sex differences in intertemporal decision-making. For instance, Eubig et al (2014) reported that following acute administration of amphetamine, females were quicker to initiate trials and displayed more impulsive choices than males. In another study, males and females were characterized as “flat” or “steep” discounters based on their task performance; “steep” female discounters displayed a greater reduction in their preference for the large, delayed reward than their male counterparts at longer delays (Koot et al 2009).…”

Gambling disorder: an integrative review of animal and human studies

“…These tasks provide rodents with a choice between a smaller, immediate reward or a larger delayed reward. Alterations in DA signaling alter this choice; however, the effects of amphetamine on impulsive choice are complex and vary with sex, strain, and paradigm . D 1 antagonists, as well as dopaminergic lesions to the dorsolateral striatum or the nucleus accumbens core, increase impulsive choice in delay‐discounting tasks in rodents, resulting in choice of the smaller nondelayed reward more often .…”