Grant: Project Grant

If we knew why some individuals are catastrophically affected by addictions, whereas others are able to simply enjoy addictive drugs and past-times recreationally, we would be able to design effective treatments to help vulnerable individuals. Whether someone is dependent on a chemical substance like cocaine, or has developed a behavioural addiction such as gambling disorder, the maladaptive choice to pursue the addiction at the expense of other goals lies at the heart of the problem. Indeed, individuals with an addiction disorder, or who later develop problems with addiction, score poorly on laboratory-based decision-making tests such as the Iowa Gambling Task (IGT) that involve the weighing of costs and benefits. One hypothesis is that decision-making impairments may be compounded as the addiction develops because of the way in which addictive drugs, and also engagement in addictive behaviors, affect brain function, biasing the decision-making process in favor of the addiction. Choosing to abstain from the addictive substance or behavior then becomes increasingly difficult. Based on the IGT, we have successfully developed an animal model of "real-world" choices: the rat gambling task (rGT). In both the human and animal tests, subjects choose between four different options, each of which is associated with different amounts of potential reward and loss. By avoiding high-risk, high-reward options, subjects can maximise gains. Most rats develop this optimal strategy, although some animals instead favour the risky options. These risk-preferring rats are uniquely and adversely affected by taking cocaine - their decision making gets worse and they show increased drug-seeking in withdrawal indicative of greater relapse risk. We now want to use this model to understand how the brains of optimal-choosing versus risk-preferring rats differ, why such differences lead to greater addiction vulnerability, and harness that knowledge to pilot potential therapies for addiction.