Fine-tuning Muscarinic Cholinergic Transmission in Alcohol Use Disorder.
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Abstract
Alcohol use disorder (AUD) is a devastating medical condition that affects millions of people around the world. Despite intensive research to investigate the pathophysiology of AUD, only a small number of medicines ever reach the market with many failing the barriers of phase II and phase III clinical trials (1). The scarcity of therapeutics for AUD is unfortunate but may reflect the traditional reliance of translational research on the reinforcing properties of alcohol and attempts to understand the processes of tolerance and withdrawal as reasons why people engage in excessive alcohol consumption. As categorized in recently revised versions of the Diagnostic and Statistical Manual of Mental Disorders (DSM – IV and V, APA) (2), AUD not only encompasses a loss of control over alcohol intake, and development of tolerance and withdrawal symptoms, but also the prioritisation of alcohol-related activities over intensifying personal and other harms. The recognition of AUD as a disorder of maladaptive choice, no different to other addictions (2), has helped pave the way for a new generation of procedures in rodents to assess compulsive drug-related behaviors (3) and with it, a more refined specification of the neural circuitry underlying the persistence of alcohol seeking (4).
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1873-2402