title: 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 no 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.
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL 61802, USA. Electronic address: eubig@illinois.edu.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Eubig
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL 61802, USA.
authors.forename: Terese E
authors.initials: TE
authors.lastname: Noe
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Stan B
authors.initials: SB
authors.lastname: Floresco
authors.affiliation: Department of Behavioral Sciences, Christian Brothers University, Memphis, TN 38104, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Sable
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL 61802, USA; Neuroscience Program, University of Illinois, Urbana, IL 61802, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Schantz
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant; D003913:Dextroamphetamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D005475:Flupenthixol / Q000494:pharmacology; D006801:Humans; D007175:Impulsive Behavior / Q000523:psychology*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D012054:Reinforcement, Psychology; D012727:Sex Characteristics
chemical_list: D018492:Dopamine Antagonists; D005475:Flupenthixol; D003913:Dextroamphetamine
keywords: Amphetamine; Delay-discounting; Flupenthixol; Impulsivity; Sex differences