Conclusions and future directions
RBCBs occur in many neuropsychiatric disorders and may even be helpful in defining them. Over the last decade, the consideration of RBCBs as important factors in the development of alcohol addiction has enriched and strengthened the field of inquiry regarding AUD and opened new avenues of research. To further define the relationships between RBCBs and AUD, in this review, we have advocated a psychological approach based largely on cognitive and learning theories, which combined with neural and neurochemical analyses may facilitate our understanding of this disease. We have also highlighted the development of translational tools, which herald a new phase of research in this field, that will more readily make contact between the clinic and basic neuroscience. We have also described the effects of pharmacological manipulations, as a multi-level analysis of RBCBs may identify medications that can be used for different expressions of what may, in fact, be common disorders resulting from reinforcement biased cognition. The possible ‘re-purposing’ of agents such as SSRIs and ketamine may provide an initial impetus for this enterprise. Finally, we also mentioned the concept of endophenotypes, as a focus on individual differences in this diverse disorder may inform genetic approaches to understanding its aetiology. Based on available knowledge, it seems that using rodent-based models, such as the preclinical PRL or ACI, can help to reveal neurobiological processes that modulate RBCBs and their role in AUD. This in turn may help to reveal novel drug targets for improved and personalized treatments. Although we hope this review has provided enough evidence to support the validity of the claim that RBCBs can determine the trajectories of alcohol addiction, there are still a number of outstanding issues that future research will need to address. First, we still do not know the degree of the causal relationship between increased/decreased sensitivity to negative/positive reinforcement as a trait and vulnerability to AUD. The development of translational preclinical tests of RBCBs should help to elucidate this issue and may help to design personalized treatments based on these cognitive variables. Second, although we know that there are distributed changes in neural activity within multiple regions of the PFC and the striatum associated with altered activity of serotonergic and dopaminergic systems that occur over the course of AUD and can persist into periods of abstinence, unfortunately, studies looking at neurochemical correlates of altered reinforcement sensitivity in this context are still limited, and further investigation in this area is needed. We also still need more detailed pharmacological studies using drugs with known profiles in humans to understand the value of targeting RBCBs in AUD. It will be highly desirable to use voltammetry, optogenetics, or other biosensors and electrophysiological measures to characterize neuronal pathways and to elucidate the exact function and dynamic balance between cortical and subcortical regions involved in RBCBs and AUD. Finally, further conceptual and empirical development is required to provide an integrated account of the role of reinforcement sensitivity in the aetiology, development, and recurrence of AUD.