To most of us, the notion that alcohol abuse is a huge problem in American society is not a new one; but if you’re anything like me, you didn’t fully understand or really care about the scope if the issue when going through the motions of the D.A.R.E. program in elementary school or later in required health classes, and you haven’t really thought about it since. Revisiting the topic, I was taken aback. The deaths, costs, and health problems attributed to alcohol abuse and alcoholism in the United States are enormous, effecting approximately 14 million people and costing $184 billion a year, according to the Tenth Special Report to the U.S. Congress on Alcohol and Health in 2000. For the U.S. population of that time, that was about 1 in 20 people effected… and that’s still a boatload of money. Advancement in the understanding of the pathophysiology and neurochemical pathways of alcohol abuse disorders has taken strides in recent years, but the questions of treatment method and viability still loom largely unanswered. What is the most effective target for pharmacological treatment? Should neurochemical means even be used in the treatment of alcoholism?
In alcoholism, alcohol preference and reinforcement seems to occur as a result of ethanol’s interaction with the dopaminergic (DA) signaling system. Ethanol decreases GABAergic activity; GABA is an inhibitory neurotransmitter, so a decrease in it makes signal transduction easier in the neuron – in this case, DA neurons. Thus, ethanol leads to an increase of dopamine release, and dopamine receptors are activated more, increasing adenylyl cyclase activity, which increases cAMP production, resulting in increased protein kinase A (PKA) signaling, which affects many substrates downstream, including DARPP-32 and CREB. DARPP-32 activation via PKA leads to NMDA receptor phosphorylation and activation, allowing an influx of Ca2+ into the cell which activates protein kinase C (PKC), finally resulting in an increase of the reward response associated with alcohol use. The effects of CREB, on the other hand, are associated with alcohol tolerance; an increase in CREB activation results in an increase in transcription of genes containing cAMP response elements, which decreases the reward response, making it necessary to consume more alcohol for the same effect. From these findings, it is suggested that DA receptor, DARPP-32, and PKC activation increase alcohol consumption, and PKA and CREB activation decrease alcohol consumption. Effective targets for pharmacological treatments may then be DARPP-32, PKC, and CREB, whose activities are abnormal in alcoholics, thought to be caused by genetic irregularities.
Researchers definitely have some leads on where to go with neurochemical treatments, but it is still unknown how effective these may be. It has been hypothesized that it is a combination of genetics and environmental factors such as stress that drive the development of alcoholism. Not only is this a possible cause for the disorder, but the researchers go as far as to suggest that the combination of these two factors is ultimately the only cause of alcoholism. If this is true, treating one of the factors should stop the progression of the disease and effectively nullify the dependence on alcohol. I’m not sure if it’s the most effective option, but I would favor treating the psychological factors such as stress and depression before resorting to chemical means. If you’ve read my past posts, you’ve probably discovered that I’m a minimalist when it comes to pharmaceuticals. So much of the time, chemical treatments only alleviate the symptoms of a disease and don’t get to the root of the problem, creating a dependence on the treatment instead of the treatment allowing a person to live free from the disease. In the case of alcoholism, it seems to me that only an alcoholic willing to receive help will effectively be treated, and at that point the most cost effective and personally empowering form of treatment involves helping them learn to cope with stress in healthy ways and work through whatever personal problems lead them to alcohol in the first place. Programs such as Alcoholics Anonymous have been effective for many people, and with the appropriate help and care, any alcoholic should be able to gain control of their life again. Kudos to the scientific community for their advancements in so many treatments for a wide variety of issues, but I think some things are better left to the power of a person’s mind.
