Drinking doesn’t sooth the soul

Bolder, Colorado

You’re in the theater, completely engrossed. You wipe away a tear at Albert’s departure, at Bruce Wayne’s broken body, at the demise of Gotham. Then you smell the smoke. See the panic. Hear the scream.

People deal with traumatic experiences differently. Some are able to work through painful memories, eventually returning to their daily lives. Others drown in feelings of pervasive fear and hopelessness, persistently re-experiencing the trauma in dreams or in flashbacks, impairing any attempt at a normal life. People with anxiety disorders may drown in alcohol, wishing to drink their fears away.

Unfortunately, alcohol may be one of the things impairing critical brain mechanisms for recover from trauma.

Holmes et al., 2012. Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding. Nat Neurosci. 2012 Oct;15(10):1359-61. doi: 10.1038/nn.3204. Epub 2012 Sep 2.

From a neurobiological point of view, conditioned fear is a memory, linking an event or object to the biological fear response. As such, it can be encoded, strengthened, retrieved, and extinguished.  Extinction of a memory is not really “forgetting” it – it doesn’t erase the fear memory trace in the brain. Instead, the brain learns a new association, that whatever you were afraid of (worms!!!) is actually harmless – this new memory trace, thought to be encoded by the medial prefrontal cortex (mPFC), competes with the conditioned fear memory when you’re re-exposed to the source of terror. If it wins, the fear memory is not expressed – that is, you wouldn’t experience the terror associated with the trigger.

Chronic alcohol use is known to affect the mPFC, changing its size, neuron number and activation, leading to deficits in attention and higher cognitive function. Given mPFC’s critical role in fear memory extinction, would heavy drinkers be more vulnerable to anxiety disorders following a traumatic event?

Researchers doused mice with vaporized alcohol with a schedule mimicking cycles of “heavy drinking” as seen in alcoholism, with a total amount roughly equivalent to twice the legal driving limit in humans. The mice were allowed to rest for two days to nurse their hangovers, and then were trained to fear a tone by pairing the tone with an electric foot shock.  As it turns out, these alcoholic mice learned to fear the tone as fast as normal mice, showing no problem with memory encoding.

To extinguish the memory, the researchers played the tone again and again without the foot shock. Compared to normal mice, the alcoholic ones lacked behind in learning this new memory, although they eventually caught up. However, when both groups were shocked again with the tone (reinstatement), the alcoholics clearly showed greater freezing – meaning that the newly encoded extinction memory was not as strong or as easily recalled as the original fear memory . On the other hand, these alcoholic mice didn’t differ from their normal littermates in tests for general (non-tone related) anxiety, fear or motor performance, meaning that fear retention is specific to the tone.

So what mediates this behavior? Turning to the mPFC, researchers found that chronic alcohol remolded the shape of neurons, so that their dendrites were longer on the non-terminal branches on one side of the neurons. Since dendrites are the basic units of neuronal computation, and form dictates function, researchers went on to measure directly brain activity in the alcoholic mouse with electrodes. Chronic alcohol breathing decreased neuronal activity both during later periods of extinction and extinction retrieval, hinting that mPFC activity is greatly suppressed.  The authors went on to show that a type of receptor generally thought to be involved in learning and memory, the NMDA receptor, was also malfunctioning, giving lower currents than usual. In fact, by inhibiting just the NMDA receptor with a drug in normal mice, the researchers were able to mimic the extinction deficiency as seen in alcoholic mice.

This study suggests that chronic alcohol users if subjected to traumatic experiences, may be unable to efficiently deal with the associated fear and may be more at risk for developing anxiety disorders. While the study makes a good case for the dysfunction of mPFC in extinction deficits, it also begs the question: what about the hippocampus? Buried deep inside the brain, the hippocampus is long known to be the center of memory processing. Previous studies in brain slices (not animals) have also shown that alcohol exposure can inhibit NMDAR currents, so it’s conceivable that hippocampus is also playing a role. Another question that comes to mind is whether the perceived deficit in extinction is actually a deficit in “updating” the existing memory – that is, a decreased ability to flexibly learn and retain an opposite association when there is a similar memory present.

Regardless, this study adds to the pool of data that we currently have on the factors that predispose people to anxiety problems following traumatic experiences. While the study won’t make me give up on weekend happy hours, it might make me pause and think twice before I reach for that second bottle of weekday beer.

Holmes A, Fitzgerald PJ, Macpherson KP, Debrouse L, Colacicco G, Flynn SM, Masneuf S, Pleil KE, Li C, Marcinkiewcz CA, Kash TL, Gunduz-Cinar O, & Camp M (2012). Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding. Nature neuroscience, 15 (10), 1359-61 PMID: 22941108


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