ORLANDO – It is a good idea to routinely ask patients–particularly those with risk factors for dependence–about their alcohol use, George F. Koob, Ph.D., said at a psychopharmacology congress sponsored by the Neuroscience Education Institute.
However, patients are not always honest, copresenter Dr. Stephen M. Stahl pointed out. “Most of us try to screen patients for alcohol, but … I can't tell you the number of times I've been bamboozled by patients.
“In clinical practice, there are a lot of people who are heavy drinkers who do not think of themselves as alcoholics. They will be completely insulted if you tell them,” said Dr. Stahl of the department of psychiatry, University of California, San Diego, and chairman of the institute.
He and Dr. Koob, professor and chairman of the committee on the neurobiology of addictive disorders at the Scripps Research Institute, La Jolla, Calif., recommended use of the Alcohol Use Disorders Identification Test (AUDIT). However, 84% of those attending the meeting indicated they have never used the AUDIT screening tool, according to an electronic poll.
According to Dr. Koob, two neurologic systems reinforce alcohol dependence–both dopamine and serotonin pathways–and make it more difficult for people to stop drinking, and advances in neurobiology are offering new insights into how the brain is altered by alcohol use, dependence, and withdrawal.
“The neurobiology has led us where there are spectacular new targets for treatment of alcoholism,” Dr. Koob said. Rewarding effects of alcohol may be mediated by dopaminergic and opioidergic systems.
Researchers have long proposed that the pleasure provided through the mesolimbic pathway explains why people initially drink alcohol or take drugs. Dopamine is released in the front end of the brain while opioids activate the ventral tegmental area and nucleus accumbens. “So it's a combination of the opioids and dopamine effects that causes a pleasurable experience.”
Impulsive drinking, particularly in young males, is an activation of reward mechanisms driven by initial pleasurable effects, Dr. Koob said. “As a person continues to drink, the reward system gets impaired but hyperarousal in brain is set up that only alcohol will suppress. So [drinking] becomes self-medicating,” he noted.
“Those people you knew in college who could drink everyone under the table ultimately end up with a problem,” Dr. Koob said. “That starts the neuroadaptive process, so they end up needing that [higher] amount of alcohol.”
The acute double action of alcohol is to enhance γ-aminobutyric acid (GABA) and decrease glutamate, Dr. Koob said. Both dopamine and serotonin pathways may mediate alcohol dependence. The frontal cortex, amygdala, and hippocampus are the brain areas that might contribute to dependence, Dr. Koob added.
Neurobiologists have found that consumption of alcohol also may alter regulatory agents of stress, particularly increasing corticotropin releasing factor (CRF) activity and decreasing neuropeptide Y. “While you are bingeing on alcohol, you are releasing the good guys like dopamine peptides, but when you get into withdrawal, you are recruiting the bad guys–the GABA system and the CRF stress hormone,” Dr. Koob said.
“You have a double-whammy effect when you become dependent–you lose the good guys and gain the brain stress system–so you continue to self-medicate with your drug of choice.”