Abnormal Motivation


(Why you can’t think of doing anything else)

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We all want to be healthy happy people.  In order to be happy, we need the hormones and neurotransmitters that control our moods to be working optimally.  Seratonin, norepinephrine and dopamine are among the more important chemicals in our brain that need to be balanced.  Increasingly, the role of glutamate is also being recognized as crucial to our emotional health.   These chemicals all need to be running at an optimal levels; too much or too little will wreak havoc with our emotions. 


There is an important neuro-physiology concept call TONE. A nerve left completely alone will still fire at a certain rate.  It will release a certain quantity of neurotransmitter.  This steady baseline secretion of transmitter is call tone.  Many processes will transiently increase or decrease nerve activity from baseline.  The nerves have evolved to adapt to any outside stimulation in order to return activity as close to baseline as possible.  This is the reason people become physically dependent on drugs with chronic exposure.


Despite the tendency to maintain baseline activity, it is part of normal physiology that there will be transient increases in activity and neurotransmitter release.  This is especially true with dopamine.  Periodic pleasures, such as orgasm or good food, will transiently increased dopamine.  In fact, such periodic increases in dopamine are likely necessary for optimal emotional health. 


It is not only experiencing  pleasure that release dopamine;  even the anticipation of a pleasurable activity will increase dopamine.  This makes perfect sense for the survival of the organism and species.  If I anticipate finding a good meal or having sex, I will have a dopamine surge in my brain.  I will therefore maintain this thought in my head.  This will motivate me to perform the activities necessary to secure that meal or sexual encounter. 


I enjoy eating, reading, doing crosswords and spending time with my family.  I look forward to playing tennis.  Whenever I look foward to these activities, the dopamine surges in my brain.  If we did not look forward to something we could be clinically depressed.


An important area involved with anticipation may be located in a nerve tract that ori in ginates in the prefrontal cortex and goes to the Nucleus Accumbens.  The prefrontal cortex (PFC) is the area of the brain where complex behavior is initiated.  The nucleus Accumbens (NA) is the pleasure center of the brain where dopamine is released.  This is where the drugs of abuse work. 

This nerve tract releases glutamate in the NA.  The glutamate interacts with a specific type of receptor (the NMDA receptor) that results in a greater release of dopamine.  This makes a thought stay in our brain.  Without glutamate, we would look foward to anything

Glutamate is essential for addiction behavior.  Studies have demonstrated that the rodents born with genetic defects that prevent certain types of glutamate responses are unable to become addicted. 


The release and interactions of glutamate and dopamine in this fashion motivates our behavior.  They are the reasons we look forward to doing the things we like to do.  Undoubtedly, this nerve connection is, and will continue to be, the subject of intense research.


We all look forward to doing a variety of fun and pleasurable activities.  What about the addict?  A typical young man will look forward to a possible sexual encounter.  However, the average young male addict will compareably less interested in sex as the average male non-addict.  Imaging studies show a decrease in metabolism in the relevant brain areas.  In many realms, we see that the person who is addicted, or in early recovery, is not interested in a lot things.  They often describe a boredom or fatigue. It is not a fatigue where they sleep; rather, they just are not interested in doing anything.  It is a situation similar to depression. 


Animal can also be trained to anticipate reward.  Their brains can be studied during these behaviors. Glutamate and Dopamine surges in the NA are part of this process.  However, rodents who were addicted to cocaine and are now in recovery have less of a surge of these chemicals.  They just can’t get excited about any reward ( such as food) that is not drug related. 


Important abnormalities are observed when these PFC to NA nerves are examined in rodents that are in early recovery. The cells that secrete glutamate are less likely to fire.  These changes have been partly attributed to intra-cellular changes of specific proteins.  When these changes are reversed in the laboratory, anticipatory behavior returns to normal. 

What is really amazing is that when anticipatory behavior is normalized, addictive behavior is reduced.  Since the brain is busy anticipating non-drug rewards, it has less time to anticipate drug rewards, so drug seeking is reduced.

The previously mentioned dysfunction in the brain is associated with less activity of the cells in the NA.
 This is not healthy.  We need to have optimal activity in this area for optimal emotional health.  We will be depressed and irritable.  We will want to relieve this situation.

We will be subsequently be more likely to lose control of any thought or behavior that increases glutamate/dopamine action in this area.


The anticipation of using drugs seems to be one of the few things that is able to overcome this baseline inhibition of glutamate/dopamine action.  Therefore using drugs is one of the few things that we look forward to.

It’s as if we need a certain amount of stimulation in this part of the brain.  If the only way to get it is by thinking about the drug, than that is all we will think about.  Since nothing else excites us, there is nothing to divert our attention.  We begin to obsess and our cravings increase in intensity.


One wonders why anticipation of drug use is so much stronger than anticipation of other behaviors.  This occurs because of the pathological learning that has taken place during the development of the addiction.


To sum up, hypo-function of the PFC to NA tract results is a general lack of motivation and sets the stage for obsessing about drugs.  It seems reasonable that gambling, sex and other non-substance addiction disorders may have a similar pathology.  I believe this abnormality constitutes one of the core pathologies involved with the disease of addiction


At the present time, there are no drugs to treat this problem.  In animals, manipulation of brain physiology with directly infused drugs has reversed the abnormalities.  However, these treatments remain limited to the lab bench.  I believe that time will repair this circuit to some degree.  The brain has the ability to restore itself towards normal.  This process can take months or longer.  In certain types of substance use (such as opiate and perhaps marijuana and alcohol) I believe that this process might be accelerated with the use of naltrexone. (see article)

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Stuart Wasser

March 10, 2006