ReviewTranslating the neuroscience of alcoholism into clinical treatments: From blocking the buzz to curing the blues
Section snippets
Introduction: alcohol is different
Although increasingly refined, current theories of addiction largely continue to build on two major sets of discoveries. The first of these are the findings identifying the mesolimbic dopaminergic (DA) pathway as a critical substrate for motivation to engage in exploration of the environment and pursuit of goal oriented behavior. The second set consists of observations that most, if not all, addictive drugs interact with this DA circuitry.
Combining these insights, a succession of theories have
Getting the buzz from alcohol: an opioid–DA cascade
In trying to understand to what extent alcohol interactions with classical reward pathways are a critical substrate for reinforcement of alcohol seeking and intake, several observations need to be made. Already in 1973, a seminal but often overlooked human study suggested a key role for DA in pleasurable and stimulating effects of alcohol in healthy, non-dependent volunteers (Ahlenius et al., 1973). Numerous microdialysis studies in rodents subsequently demonstrated an ability of alcohol to
Curing the blues: extrahypothalamic corticotropin-releasing hormone (CRH)
What, then, maintains excessive alcohol use under conditions when acute rewarding alcohol actions are less important? Clearly, acute tension-reducing or anxiolytic alcohol effects are likely to contribute to social alcohol use. Alcohol actions on GABA-ergic and glutamatergic transmission are major mediators of these acute negatively reinforcing alcohol effects. These mechanisms have recently been reviewed (Spanagel, 2009) and are beyond the scope of the present paper. Because only a minority of
A (not so) new kid on the block: substance P and its NK1 receptor
Clinical translation of preclinical findings validating CRH1 receptors as a target for alcoholism treatment has been slow. This is largely related to issues of medicinal chemistry and is beyond the scope of the present paper. In the meantime, we have explored whether other stress systems might act in parallel with CRH to drive excessive alcohol intake. We have been particularly interested in mechanisms that have been in clinical development for other indications, and therefore might offer
Conclusions
Alcohol use disorders are major causes of morbidity and mortality (Ezzati et al., 2002). Although spontaneous remission occurs, classical studies show that relapse occurs within a 12-month period in almost 2/3 of clinical cases in conventional treatment programs (Hunt et al., 1971). The introduction of the competitive opioid antagonist naltrexone and the functional glutamate antagonist acamprosate provided proof of concept for pharmacotherapy of alcohol addiction, but effect sizes are limited (
Conflict of interest
The authors have no conflict of interest to declare.
Acknowledgment
The research from the NIAAA Laboratory of Clinical and Translational Studies reviewed here is supported by intramural NIAAA funding.
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2021, Drug and Alcohol DependenceAlcohol-Preferring Rats and 22-kHz Negative-Affect Ultrasonic Vocalizations
2018, Handbook of Behavioral NeuroscienceCitation Excerpt :P rats originated from a closed colony of Wistar rats and HAD-1 rats are the result of selective crossbreeding of the N/Nih heterogeneous stock of rats (Bell, Rodd, Engleman, Toalston, & McBride, 2014; McBride, Rodd, Bell, Lumeng, & Li, 2014). Nevertheless, rats of these varied origins respond to alcohol in manners similar to human alcohol abusers (Bell, Rodd, Lumeng, Murphy, & McBride, 2006; Heilig et al., 2010; Vengeliene, Bilbao, Molander, & Spanagel, 2008) and in line with all (or most) of the proposed criteria for an animal model of alcoholism (McBride et al., 2014; McBride & Li, 1998). On the other hand, rats selectively bred for low alcohol consumption (e.g., NP, LAD lines) show a resistance to alcohol intake (Murphy et al., 2002).
High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking
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