Uncertainty exposure causes behavioural sensitization and increases risky decision-making in male rats: toward modelling gambling disorder

Uncertainty exposure causes behavioural sensitization and increases risky decision-making in male rats: toward modelling gambling disorder


J Psychiatry Neurosci 2017;42(6):404-413

Fiona D. Zeeb, PhD; Zhaoxia Li, BSc; Daniel C. Fisher, BA; Martin H. Zack, PhD; Paul J. Fletcher, PhD


Background: An animal model of gambling disorder, previously known as pathological gambling, could advance our understanding of the disorder and help with treatment development. We hypothesized that repeated exposure to uncertainty during gambling induces behavioural and dopamine (DA) sensitization — similar to chronic exposure to drugs of abuse. Uncertainty exposure (UE) may also increase risky decision-making in an animal model of gambling disorder.

Methods: Male Sprague Dawley rats received 56 UE sessions, during which animals responded for saccharin according to an unpredictable, variable ratio schedule of reinforcement (VR group). Control animals responded on a predictable, fixed ratio schedule (FR group). Rats yoked to receive unpredictable reward were also included (Y group). Animals were then tested on the Rat Gambling Task (rGT), an analogue of the Iowa Gambling Task, to measure decision-making.

Results: Compared with the FR group, the VR and Y groups experienced a greater locomotor response following administration of amphetamine. On the rGT, the FR and Y groups preferred the advantageous options over the risky, disadvantageous options throughout testing (40 sessions). However, rats in the VR group did not have a significant preference for the advantageous options during sessions 20–40. Amphetamine had a small, but significant, effect on decision-making only in the VR group. After rGT testing, only the VR group showed greater hyperactivity following administration of amphetamine compared with the FR group.

Limitations: Reward uncertainty was the only gambling feature modelled.

Conclusion: Actively responding for uncertain reward likely sensitized the DA system and impaired the ability to make optimal decisions, modelling some aspects of gambling disorder.

Submitted Jan. 5, 2017; Revised May 25, 2017; Accepted June 16, 2017; Early-released Aug. 23, 2017

Acknowledgements: This work was funded by an operating grant from the National Center for Responsible Gaming (NCRG) to F. Zeeb, M. Zack and P. Fletcher. F. Zeeb was also supported by a Canadian Institutes for Health Research (CIHR) Postdoctoral Fellowship.

Affiliations: From the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Section of Biopsychology, Toronto (Zeeb, Li, Fisher, Zack, Fletcher); the Department of Psychiatry, University of Toronto, Toronto (Zeeb, Fletcher); the Department of Pharmacology and Toxicology, University of Toronto, Toronto (Zack); and the Department of Psychology, University of Toronto, Toronto, Ont., Canada (Fletcher).

Competing interests: F. Zeeb previously consulted for Intervivo Solutions on an unrelated matter. None declared by the other authors.

Contributors: F. Zeeb, M. Zack and P. Fletcher designed the study F. Zeeb, Z. Li and D. Fisher acquired the data, which F. Zeeb, M. Zack and P. Fletcher analyzed. F. Zeeb wrote the article, which all
authors reviewed and approved for publication.

DOI: 10.1503/jpn.170003

Correspondence to: F.D. Zeeb, Centre for Addiction and Mental Health (CAMH), 250 College St; Toronto ON M5T 1R8; fiona.zeeb@camh.ca