Elucidating the neurobiology of problem gambling using a novel rodent slot machine task

Abstract

Gambling is an enjoyable and innocuous past-time for many, but for some it can become a maladaptive compulsion akin to drug or alcohol addiction. Despite increasing recognition that the phenomenological process underlying both substance and behavioural addictions may be similar, treatment options for problem gambling remain limited, and of questionable efficacy. Animal models offer an invaluable opportunity to not only study the underlying neurobiology of disorders such as gambling, but may also facilitate the development of novel pharmacotherapies. To that end we have developed a rodent slot machine task (rSMT) that suggests rats share key behavioural features with human gamblers. The dopamine D2-like receptor family is critically involved in modulating animals’ performance on the rSMT. Specifically, the D4 receptor appears to contribute to animals’ attributions of salience to game-related stimuli. D4 receptors are principally located within prefrontal cortical regions and consequently represent an intriguing target for modulating higher order cognitive processes. In addition to systemic pharmacology, we have demonstrated that disruption of neural regions that are relatively rich in D4 receptors, such as the anterior cingulate and insular cortex, impact animals’ ability to accurately respond to reward-related stimuli on the rSMT; further emphasising a role for these receptors in gambling-related decision making.

Additionally, we have used the rSMT to try and model iatrogenic gambling observed in patients with Parkinson’s disease (PD). This form of compulsive gambling arises de-novo in a small but significant sub-set of patients following adjunctive therapy with D2-like agonists. Chronic administration of a D2/3 receptor agonist galvanized performance on the rSMT, a finding that could be considered translationally analogous to the compulsive play exhibited by some PD patients. These alterations in performance were accompanied by an increase in the transcription factor pCREB in the nucleus accumbens. Administration of the β-adrenoreceptor blocker propranolol, which putatively attenuates this increase in pCREB, ameliorates the compulsive-like task engagement.

Ultimately, gambling is a heterogeneous disorder that is unlikely to have a single underlying aetiology. However, these data indicate that aberrant dopaminergic signalling within the D2-like receptor family may underlie at least some of the cognitive perturbations observed in problem gambling.

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