Serotonergic and dopaminergic modulation of gambling behavior as assessed using a novel rat gambling task

Author(s): Fiona D. Zeeb, Trevor W. Robbins, Ph.D and Catharine A. Winstanley, Ph.D
Department of Psychology, University of British Columbia, Vancouver, Canada; Department of Experimental Psychology, University of Cambridge, Cambridge, UK
 

Abstract

Pathological gambling (PG) is characterized by persistent, maladaptive gambling behavior which disrupts personal and professional life.  Animal models of gambling behavior could make a significant contribution to improving our understanding of the neural and neurochemical basis of gambling and the treatment of PG.  When gambling, failing to win critically results in the loss of resources wagered as well as the absence of additional gain.  Here we have incorporated these concepts into a novel rat gambling task (rGT), based in part on the "Iowa" gambling task (IGT) commonly used clinically to measure gambling-like behavior.  Rats choose between four different options to earn as many sugar pellets as possible within 30 mins.  Each option is associated with delivery of a different amount of reward, but also with a different probability and duration of punishing time out periods during which reward cannot be earned.  The schedules are designed such that persistent choice of options linked with the larger rewards result in fewer pellets earned per unit time.  Rats learn to avoid these risky options to maximize their earnings, comparable to the optimal strategy in the IGT.  Both d-amphetamine and the 5-HT1A receptor agonist 8-OH-DPAT impaired task performance.  In contrast, the dopamine D2 receptor antagonist eticlopride improved performance, whereas the D1 receptor antagonist SCH23390 had no effect.  These data suggest that both serotonergic and dopaminergic agents can impair and improve gambling performance, and indicate that the rGT will be a useful tool to study the biological basis of gambling.

Commentary

by Fiona D. Zeeb, corresponding author

By using a novel rat gambling task (rGT) to we observed that animals are able to successfully "play the odds" and can incorporate multiple factors into making gambling-like decisions.  A unique property of the rGT is that it incorporates losses, as opposed to just a failure to win.  The rGT is partially based on the ‘Iowa' Gambling Task (IGT), commonly used in clinical research to measure gambling-like behavior.  In the rGT, animals played against the clock in each 30 min session to gain sugar pellets.  Animals chose from four different options, each of which is associated with a different amount of reward (one to four pellets), and a different probability of losing and incurring a time-out during which reward could not be earned.  These frustrating time-outs are the equivalent of losses in the IGT.  In both the rodent and human versions, larger reward options are associated with heavier punishments.  Animals, like humans, adopt the optimal strategy and select mainly from options associated with smaller immediate gains, but also smaller losses in the long-term.  Enhanced performance on the rGT was observed when dopamine D2 receptors were blocked; animals increased their preference for  the most advantageous option.  In contrast, decreasing levels of serotonin produced an increased choice of the disadvantageous options.  Similar impairments on the IGT have been observed in patients with pathological gambling, who likewise show decreases in peripheral measures of serotonin.  These data suggest that the rGT could be a translational tool that will be useful in elucidating the neurobiological basis of gambling in addition to other impulse control disorders.

We haven't tried fluoxetine/ citalopram yet, but it's one of the experiments we're hoping to do next year. I agree that the results of such an experiment could be very informative, especially given that SSRIs are currently prescribed for pathological gambling. Ideally, we'd look at both chronic and acute administration. Hopefully we can find a friendly pharma company to supply us with the compounds! Best wishes, Catharine
Catharine Winstanley
Posted: Sep 17, 2009 2:43 PM
I wonder if you or anyone else has tried a 5HT uptake inhibitor (fluoxetine, citalopram) in this test? Might stimulation of other 5HT receptor subtypes have beneficial effects? Thank you for your insights. Bill Carlezon
Bill Carlezon
Posted: Sep 09, 2009 3:31 PM
Following on to Fiona's comments, although we work with Long Evans rats, I'd guess that Sprague-Dawley animals would be able to learn the task just as effectively. The albino strains tend to have poorer eyesight which can be a problem for attentional tasks where the rats have to spot a visual stimulus of brief duration. However, in the rGT, the stimulus lights are on for 10s so this wouldn't be an issue. It would be interesting to see whether the Sprague-Dawley rats show the same preferences as Long Evans. We're happy to send our MedPC code out to other groups who would like to use the task. Our email addresses can be found in the paper.
Catharine Winstanley
Posted: Jul 18, 2009 2:10 PM

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