The Neurobiology of Addiction: The Alcohol Craving Circuit

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Dramatic results from experiments targeting a specific brain circuit that neuroscientists believe plays a crucial role in intense alcohol cravings suggest that one day we may develop medications that can abolish those cravings. Sensory properties of alcohol—specifically, its odor and taste—are considered powerful stimuli to relapsing and hence pose a serious obstacle to long-term recovery. Most patients with alcoholism relapse within one year of abstinence. The promise of targeted therapies—whether gene or drug—that can essentially turn off cravings, like the flip of a switch, would be a powerful therapeutic approach to the treatment of alcohol use disorders.

Negative Reinforcement and Relapse

Neuroscientists frame adaptive and maladaptive behaviors in terms of basic stimulus-response reinforcement. When a given stimulus – such as alcohol – produces a beneficial effect – whether euphoria or avoidance of anxiety – it becomes reinforced and motivates individuals to continue to seek it.

Reinforcements can be either positive or negative.

Positively reinforced stimuli are sought because they induce pleasure. Negatively reinforced stimuli are sought because they enable an individual to avoid unpleasant feelings, such as anxiety, or alcohol withdrawal. Intense alcohol cravings that persist in individuals who have been abstinent for long periods of time are considered negatively reinforced alcohol-encoded memories.

Many people living with an alcohol use disorder continue drinking to avoid the physiological and emotional symptoms of alcohol withdrawal. Given that the physiological symptoms diminish relatively soon after abstinence begins, the emotional symptoms – the return of anxiety, irritability, or depression – explain the persistence of alcohol cravings that lead to relapse.

The Alcohol Craving Circuit

Neurons (a.k.a. brain cells) communicate through chemical and electrical signaling (neurotransmission) to produce diverse behaviors. When a certain behavior becomes reinforced – regularly repeated – it strengthens the circuits specific to that certain behavior.

That’s how the brain literally encodes human behavior in its circuits.

In animal studies, neuroscientists can effectively isolate the brain/neural circuits associated with reinforced (stimulus-response) behaviors. In the case of alcohol cravings, researchers use operant conditioning on rodents that simulate alcohol dependency. Next, through sophisticated procedures that literally “light up” specific neurons and their location in the brain, researchers can match subjective feelings such as alcohol craving with the specific brain circuits that create them.

A convergence of evidence points to a brain circuit communicating from the Central Nucleus of the Amygdala (CeA) to the Bed Nucleus of the Stria Terminalis (BNST). Among the functions of the amygdala region is the association of events like drinking alcohol with emotions like pleasure. The BNST region of the brain generates emotional and behavioral responses to stress. Both of these regions are part of the limbic system, which is home to motivation, behavior, long-term memory, the sense of smell, and emotion.

One specific neurotransmitter that plays a key role in the CeA-BNST circuit is called corticotropin-releasing factor (CRF). CRF is better known in a very different role as a neurohormone produced by another region of the brain, the hypothalamus. In that region, it activates the primary stress-response pathway called the hypothalamic–pituitary–adrenal (HPA) axis. Interestingly, CRF’s role as a neurotransmitter in the CeA-BNST circuit appears to be distinct from its functions as a blood-borne stress hormone.

This may very well be key to understanding the brain’s alcohol-craving circuit.

The Flip of a Switch

Scientists at Scripps Research Institute – setting out to further explore the characteristics of the alcohol craving circuit (CeA-BNST) – published astonishing results. Using lasers as a reversible switch to block the transmission of CRF specifically in the alcohol craving circuit in alcohol-dependent rats, the Scripps scientists reported their motivation to ingest alcohol during withdrawal completely disappeared. Moreover, blocking the CRF signal reduced some physiological symptoms of withdrawal, such as shaking. Even more remarkable was the discovery that when the lasers were shut off and CRF signaling in the alcohol craving circuit was flipped back on, the craving returned.

The Scripps study also suggests that in the future, with more basic research on the neural underpinnings of alcohol craving, we may develop direct means for reversing the powerfully reinforced neural circuits that drive alcohol-seeking behaviors.

At present, this research is being conducted in the rodent model, which means we have to wait for scientists to replicate these findings in humans. Nonetheless, this breakthrough is inspiring for many struggling with the uncomfortable emotions that often lead to relapse.