ONE of the BIOLOGIC CAUSES OF ADDICTION

   ABNORMAL DOPAMINE METABOLISM

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Recent studies have begun to point to reasons that persons with substance abuse disorders might be biologically predisposed to their problems.  I do not mean to disregard the psychosocial and spiritual aspects of this disease that I feel are very significant.  However, biology does play a major role in the cause of this disease.  I apologize in advance for the technical aspects of this article and have simplified (and even over simplified) whenever I could.

In a previous article (Why we use drugs),  I outlined which part of our brain was the target of the drugs we abuse.  Specifically, there is an area called the Nucleus Accumbens ( N. Accumbens) where stimulation causes a pleasurable sensation.  For this reason, this area can be considered the ‘pleasure center’ of the brain.  This area is felt to be the main target of all drugs of abuse.  Normally much of the stimulation to this area is from a  neural tract that begins in a part of the brain call the Ventral Tegmentum (VT) and ends in the N. Accumbens.   A neural tract is a great number of nerve cells that run together. The VT simulates this tract that in turn releases dopamine into the  N. Accumbens.  The dopamine, in turn, stimulates the nerves that begin in this area.  This causes pleasure.  Almost all drugs of abuse will increase dopamine in the N. Accumbens and cause pleasure.  That is why they are abused.

Proper function of this neural tract  is necessary  in order for the N. Accumbens to function at a normal level of activity.  A  lack of proper activity in the N. Accumbens has unproven consequences but it seems reasonable that there would be less sensations of pleasure.  This could cause chronic depression since experiencing appropriate degrees of pleasure are necessary for emotional health.   Also, just as a hungry person is less able to resist food,  a person with a chronic low N. Accumbens activity may be less able to resist any activity or drug that increases the sensation of pleasure.  They will be hungrier for pleasure compared to persons with normally functioning pleasure centers.   This hunger predisposes the person towards use of addictive medication.

At this time, I am aware of no studies that clearly document malfunction of this tract in humans.  However, there have been studies in laboratory rats that are very significant.  While we are much different than rats in many ways, we are also very similar.  The VT and N. Accumbens areas are also found in the rat brain and have similar roles.  One advantage of looking at laboratory  rats is that they almost identical twins to one another.  They are alike in every way except in those specific ways you breed them to be different.  Well, some people decided to breed alcoholic rats.  This was done by taking the rats in each generation that showed the most liking for alcohol and allowing them to make more rats.  This was done for many generations.  To contrast with these, abstinent rats were also bred over several generations.   They differed in their appetite for alcohol but, otherwise, were identical to the alcoholic rats.  It turns out that the rats more likely to abuse alcohol are also more likely to abuse other substances compared to  their abstinent cousins.  Therefore, scientists were able to breed rats that were predisposed to addiction to all types of substances.

The brains of the alcoholic and abstinent rats were compared before there was any exposure to alcohol (not even uterine exposure prior to birth). There were significant differences.  These differences were specifically located in this tract from the VT to the N. Accumbens.  It seems that, in the alcoholic rats, the nerve cells were scrawnier.  Also, the ability to get the dopamine,  needed to stimulate the N. Accumbens, to the right part of the nerve was impaired.  It seems reasonable to assume that the  abnormalities in these nerve cells result in less dopamine being available in the N. Accumbens and therefore less activity in this area.  Therefore, these rats might be born with less pleasure sensation and a greater hunger for pleasure.

Other studies have shown that when you force the abstinent rats to drink (or use other drugs), they acquire similar abnormalities of these same nerve tracts.  The nerves appear scrawnier and more disorganized compared to their twins who were not exposed to alcohol.  Even one year after the last exposure to alcohol, the nerves were still abnormal.  Since rats only live for two years, it is possible that this nerve abnormality is a permanent condition.  The conclusion is that alcohol and drug exposure can damage a normal pleasure center.  This may lead to a chronic condition where the rat acquires a hunger for pleasure.

Does the same thing happen in humans?  There is no way to test this possibility at this time.  However, we know that there is a subset of substance abusers that develop their problems very early; this group tends to have a very high prevalence of substance abuse in their family history.  It seems reasonable that some sort of genetic predisposition exists. A hereditary abnormality resulting in less N. Accumbens activity and pleasure might be an explanation for this. 

Similarly, there are those who do not have an obvious problem early in their lives.  However, they develop progressively worse problems as the years and alcohol exposure go on.  This pattern does not run in families to the degree that the other pattern does.  A process where continued drug exposure leads to a gradual reduction in N. Accumbens activity may explain this pattern of disease.

A purist may argue that we are far from proving that N. Accumbens underactivity contributes to addictive tendencies.  And, they would be right.  As we learn more, we are finding other biologic abnormalities that predispose toward addiction.  Yet, it is an intriguing possibility.  Remember, even seizures were once relegated to being psychiatric symptoms or signs of demonic possession.  As we learn more about the brain, more and more of psychiatric illness become explainable as biologic abnormalities.  Hopefully, as research continues to uncover the biologic abnormalities that lead to addiction, the stigma of addiction, and the inequities that people seeking treatment experience,  will begin to disappear.

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S. Wasser
February 5, 1998