Grant: Operating Grant

As opportunities to gamble continue to grow in our society, pathological gambling (PG) is increasingly recognised as a significant public health concern. However, effective treatments remain elusive. Among those who seek treatment for PG, compulsive engagement in slot machine play is the most commonly reported gambling activity. Psychologists have suggested that one reason why slot machines can be so "addictive" is due to the prevalence of near-miss events i.e. when 2 out of 3 stimuli match on the payline. Although people find these experiences frustrating, the occurrence of near-misses can galvanise further game play, and these stimuli also activate similar brain areas as true wins. Helping subjects to reclassify near-misses as losses, rather than wins, can decrease the desire to play a slot machine. The development of pharmacological treatments which reduce the power of near-misses to drive slot machine play could therefore represent a significant advance in treating this form of PG. To study the neurobiology underlying the near-miss effect, we developed a rat model of slot machine play, and have found that dopamine D4 receptor antagonists selectively decrease the degree to which rats respond to losses as if they were wins. Dopamine is a brain chemical that plays a critical role in signalling how motivated we are to earn rewards, and the addictive nature of drugs like cocaine has been attributed to their ability to increase dopamine levels. D4 antagonists could therefore represent a very promising treatment for compulsive slots play. We want to follow-up on these findings and determine where in the brain these D4 antagonists are acting to produce such beneficial effects in our rat model. We also want to analyse the effects of chronic administration of D4 antagonists, to observe whether the improvement in performance is consistent over time, and also whether these drugs can reduce reinstatement of play after a period of abstinence i.e. reduce a marker of relapse.