...Hank had been dry for several weeks thanks to a radical withdrawal program, but a simple walk past Pete's Tavern on any given night almost erased his will to abstain. During the daytime he did not feel a craving for alcohol, but when he passed the bar in the evening--when he saw the warm light through the windows and heard the glasses clinking--he would be sorely tempted to run inside for a beer. Addiction researchers call this phenomenon "conditioned desire." If a person had always consumed alcohol in the same situation, an encounter with the familiar stimuli will make the feeling of need for the substance almost irresistible. Then, even after years of abstinence, consuming a single drink can set off a powerful longing to imbibe more and more... (link)
Is this real? How does this work?
First, is this real? On a list of AA slogans, #298 (out of 407) is "Don't hang around wet places and wet faces." (I'm sure there are many variations.) There is a reason it has become a slogan. Several reasons, actually. From Neural systems of reinforcement for drug addiction: from actions to habits to compulsion [Barry J Everitt & Trevor W Robbins, Nature Neuroscience 8, 1481 - 1489 (2005)]
So yeah, it is real. That leaves the question of how it works. We need to understand both conditioned desire, and (even more intriguing), the phenomenon of conditioned withdrawal...
...After a fruitless argument, Ken left. While standing on the subway platform for a train home, he suddenly began to sweat, twitch and feel sick. What he really wanted was a bottle. Before he had given up drinking, he would have automatically taken a swig whenever he faced a tense situation. After the argument, his brain--shaped by experience--expected the calming effect of alcohol. When the drug did not come, he began to suffer what experts call "conditioned withdrawal" symptoms...
In order to understand conditioned desire and withdrawal, we need to understand what alcohol does to the brain, and what alcohol withdrawal does.
The mechanism
for alcohol withdrawal (PDF) is well-known. Alcohol
boosts the effect of GABA (primarily at
the GABAa receptors).
GABA (image to left) is the most abundant inhibitory
neurotransmitter in the
human brain. It is like the brake on an automobile.
Chronic consumption of alcohol causes the brain to adapt.
One of the adaptations is to cut back on the production of
GABA. That is like putting your foot on the accelerator.
So if someone drinks a lot and develops tolerance to the
alcohol, it is like they have one foot on the accelerator and one on
the brake. If they stop drinking, it is like taking the foot
off the brake, leaving a foot on the accelerator. The neural
activity in the brain accelerates
rapidly, and the person develops symptoms
of alcohol withdrawal. 
Note
that the mechanism presented above is an oversimplification.
There are other systems involved, primarily glutamate
and calcium
channels. Dopamine
(image to right) is involved as well. Check the first link in
the paragraph
above for details.The mechanism for alcohol withdrawal is reasonably straightforward, but the mechanism for conditioned withdrawal is not so simple. From Kindling in Alcohol Withdrawal (PDF) [Howard C. Becker, Ph.D., Alcohol Health & Research World, Vol. 22, No. 1, 1998]
During a conditioned withdrawal response, environmental stimuli that are repeatedly associated with withdrawal symptoms (e.g., a physician’s office or hospital) may themselves become cues that trigger the neurochemical changes resulting in the physical and psychological withdrawal symptoms. Conditioned withdrawal related responses, which reflect a kindlinglike process, may represent the biological basis for cue-induced alcohol craving in these circumstances...
...AW activates the HPA axis, and the levels of hormones secreted by the adrenal cortex (i.e., corticosteroids) increase. Research indicates that this withdrawal-induced increase in corticosteroid levels is enhanced and more sustained in animals with a history of multiple withdrawal episodes (Becker and Littleton 1996). One group of corticosteroids, the glucocorticoids, influence neural excitability by interacting with certain receptors in the brain. Prolonged stimulation of these receptors as a result of elevated glucocorticoid levels in the blood may not only alter seizure susceptibility but also may produce neural damage, particularly in brain structures such as the hippocampus...
In other words, the conditioning mechanism is similar to the mechanism of posttraumatic stress disorder (1, 2, 3). So the slogan "Don't hang around wet places and wet faces" has a biological substrate. If you drink a lot, and especially if you've been in withdrawal a lot, your brain gets wired to have conditioned desire and conditioned withdrawal responses. Alcoholics with a bit of experience -- or education -- know this. They know that they shouldn't drink near-beer for the same reasons they should avoid other reminders of drinking alcohol.
Comments
Aha. This explains a lot.
You've just made me change my politics. Now I want George Bush to go back to cocaine and whiskey.
Then we can bring our troops home and begin the decade of repair that will be needed.
Posted by: Gork | June 9, 2007 8:10 PM
It may also be the case however that repeated exposure to the cues without the usual outcome (intoxication) will habituate the individual to the cue, thereby decreasing its power to trigger relapse. In some senses the animal reinstatement models do this because the animal is habituated (extinguished) to several cues (operant box, lever responding) but not others (light, tone, etc) which predict drug availability.
Posted by: Drugmonkey | June 10, 2007 12:29 PM
I am pretty sure that habituation to cues was tried in some treatment centers, and they gave up, because it did not seem to help. perhaps they were not doing it right. Perhaps they need to do it while taking d-cycloserine. Perhaps it works for some people and not others. Humans are like that.
Posted by: Joseph j7uy5 | June 10, 2007 3:25 PM
Excellent review of neurobiology of addictions. I have posted a link to your comments on www.alcoholreports.blogspot.com.
Posted by: loranarcher | June 10, 2007 11:02 PM
What about the negative reinforcement of cues, such as inducing nausea in the presence of a bar or a bottle to make the thought of drinking physically awful? I'm sure there's a lot of negative effects already linked to alcoholism, or else people wouldn't want to stop, but is there away to make the previous cues completely repulsive?
Posted by: Renaisauce | June 11, 2007 12:54 PM
The first pharmacotherapy for alcohol abuse, Antabuse (disulfiram) was approved in ca. 1951 and takes precisely this approach although it requires actually drinking alcohol to work. It works by blocking a second step metabolism of alcohol, building up a nausea-inducing metabolite (acetaldehyde) formed from initial metabolism.
This would be "positive punishment", not "negative reinforcement" btw.
Posted by: Drugmonkey | June 11, 2007 1:53 PM
Approximately 95 percent of people who quit drinking alcohol experience mild to moderate withdrawal symptoms and can usually be treated by healthcare providers on an out-patient basis, but five percent experience severe withdrawal symptoms and must be treated in a hospital or a facility that specializes in detoxification.
Posted by: Deepak | February 7, 2009 7:41 PM
Now a days it’s a very critical issue as we all are aware by this issue but we are unable to do something about these types of issues. Mostly youngsters are having alcohol and other types of drugs. I think we should think about these types of issues otherwise our coming generation will have to face lot's of problems. Great Post i look forward to reading more.
Sydney
Alcoholism Information
Posted by: Sydney | February 23, 2009 2:37 AM