Abstract
Gambling is an addictive disorder with serious societal and personal costs. To-date, there are no approved pharmacological treatments for gambling disorder. Evidence suggests a role for dopamine in gambling disorder and thus may provide a therapeutic target. The present study therefore aimed to investigate the effects of selective antagonists and agonists of D2, D3 and D4 receptors in a rodent analogue of the Iowa gambling task used clinically. In this rat gambling task (rGT), animals are trained to associate different response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. As in the Iowa gambling task, the optimal strategy is to avoid the tempting high-risk high-reward options, and instead favor those linked to smaller per-trial rewards but also lower punishments, thereby maximizing the amount of reward earned over time. Administration of those selective ligands did not affect decision making under the rGT. Only the D4 drug had modest effects on latency measures suggesting that D4 may contribute in some ways to decision making under this task.
Highlights
Gambling disorder is subsumed under the ‘substance-related and addictive disorders’ section in the recently released DSM-5 [1]
Dopamine Receptors and Gambling treatments exist for gambling disorder, and dopamine agents may provide some efficacy in this regard
D3 receptors are localized to the isles of Calleja, mammillary bodies, accumbens shell, frontoparietal cortex and the substantia nigra/ventral tegmental area (SN/ VTA), basolateral amygdala and lateral habenula [14] [15,16,17], while D4 receptors are found in cerebral cortex, amygdala, hypothalamus and pituitary, sparsely in the basal ganglia [18] [19,20,21] [22] and the retina [23]
Summary
Gambling disorder is subsumed under the ‘substance-related and addictive disorders’ section in the recently released DSM-5 [1]. There are 2 families of dopamine receptors, the D1-like (D1 and D5), and the D2-like (D2, D3, D4) Of these receptors, the D2 subtype has been used as a treatment for disorders such as schizophrenia, albeit with debilitating side effects [8]. The D3 and D4 subtypes may be promising as targets devoid of non-selective effects [9,10,11]. In this regard, both the D3 and D4 subtypes have restricted localization in the brain, consistent with a role in cognition and emotion [12, 13]. D3 receptors are localized to the isles of Calleja, mammillary bodies, accumbens shell, frontoparietal cortex and the substantia nigra/ventral tegmental area (SN/ VTA), basolateral amygdala and lateral habenula [14] [15,16,17], while D4 receptors are found in cerebral cortex, amygdala, hypothalamus and pituitary, sparsely in the basal ganglia [18] [19,20,21] [22] and the retina [23]
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