A heavy alcohol drinker attempts to take a day off with his body with shaky hands, heart palpitations, anxiety, and headaches. This is why people with alcohol use disorders are experiencing profound emotional distress because they have no choice but to quit. Now, scientists at Scripps Research have made significant improvements in understanding the basis of alcohol withdrawal in the brain.
When scientists block CRF in rats or mice addicted to alcohol, the animals drink less. According to the new study, scientists believed CRF is produced by neurons in the central nucleus of the amygdala. At least in micethese cells arent required for alcohol withdrawal or alcohol dependence.
Because this is one of the motivational drivers of excessive alcohol drinking, Candice Contet, PhD, is an associate professor at Scripps Research. These findings werent what we expected, but they help us get closer to understanding alcohol addiction and the role of CRF.
During alcohol withdrawal, CRF levels are increased in rats and mice''s central nucleus, as well as as in response to other psychological stresses. Pharmaceutical companies are actively investigating how to target CRF signaling in order to treat a variety of psychological disorders including alcohol addiction. However, findings in humans have been inconclusive, and scientists have failed to pinpoint which cells in the brain release CRF during alcohol withdrawal.
The researchers found that cells in the central amygdala produced the CRF necessary for alcohol withdrawal. In a new study, they activated and blocked these amygdala-residing neurons in various ways designed to replicate cycles of alcohol dependence. This was surprising because it implied that the CRF detected in the central amygdala was not being developed in the area.
According to Contet, activating these neurons within the central amygdala isn''t sufficient or necessary for the rapid growth of drinking in mice. This means that the CRF is coming to the central amygdala from somewhere else in the brain. Other neurons in the brain are known to produce CRF, but the team doesn''t yet know which one might be involved in alcohol dependence.
These findings were surprising, but they highlight the complexity of the CRF system and the changes in brain circuitry that occur following chronic alcohol exposure, according to Melissa Herman, a former Scripps Research postdoctoral researcher who was the first author of the new paper.
Another unexpected observation is that the CRF neurons were not organized the same way in mice brains as they were in rat brains. This also suggests that the amygdala neurons in question have been found to be necessary for alcohol withdrawal in rats, but not in mice.
When it comes to human consequences, our data must be taken with a grain of salt. It''s very important that rats and mice are inferred in more work to determine whether these two components are beneficial to humans.
The group is planning experiments to understand the differences in CRF between rats and mice, as well as identify which other neurons in the brain might be involved in its production during alcohol withdrawal.