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.