Gradual and Deadly –

APRIL 26, 2020 – On the other hand, Koob explained, mental health conditions can also complicate alcohol abuse treatment. Alcohol use disorder (AUD) causes an enormous amount of human suffering, loss of productivity and cost to the medical care system and the US economy.

There are 3 stages that make up the heuristic framework—a binge/intoxication stage, a withdrawal/negative affect stage, and a preoccupation/anticipation (craving) stage representing the domains of incentive salience, negative emotional states and executive function. These stages has allowed identification of key neurocircuits: basal ganglia, extended amygdala, and frontal cortex, respectively, that underlie addiction to alcohol. 

Alcohol tends to overpower the reward function of endogenous opioids and dopamine, while driving incentive salience and engaging pathological habits through molecular and neurocircuitry neuroadaptations within the basal ganglia. Alcohol withdrawals can produce a negative emotional state—hyphedonia, dysphoria, anxiety, irritability, and sleep disturbance.

The negative emotional state that drives negative reinforcement might derive from the within-system dysregulation of key neurochemical circuits that mediate incentive-salience reward systems in the ventral striatum and from the between-system recruitment of brain stress systems in the extended amygdala.

 Significant overlap in the engagement of circuits mediating brain emotional pain and physical pain may help explain the role of alcohol in “deaths of despair,” contributing to 15-20% of all drug overdoses, 26% of all suicides, and 50% of liver disease deaths.  


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