Biology 103
2000 Second Web Report
On Serendip

The Root of Reward of Reward Deficiency Syndrome

Shah Aashna Hossain

"What has spawned a new way of looking at addiction is the fact that many of the potent motivational, and hence addictive, properties of different substances seem to involve a common neurochemical actionÍ" a "relationship between neurotransmitters, their receptors in the brain and addictive action."

- Bozarth, director of the Addiction Research Unit in the Department of Psychology in the College of Arts and Letters (1)

In the Hebb laboratory of McGill University in 1954, research psychologist James Olds was running a series of experiments involving the neurological alerting process of rats (2). Accidentally, he placed some electrodes inside the rats' limbic system - a part of the brain containing a group of structures that play a role in emotions. The brain was wired in a way that this area could be stimulated when the rat pressed on a lever. Curiously enough, the rats went back to pressing the connected lever time and time again - even up to 5,000 times per hour. They even denied themselves everything except sleep for the stimulation provided. Carried out in the medial hypothalmus region of human brains, this experiment was found to provide its subjects with feelings resembling orgasmic sexual arousal. And if certain other areas of the brain experienced stimulation, negative thoughts were eliminated and a feeling of light-headedness would occur. Thus was born the concept of the brain's reward pathway. In other words, the discovery that "pleasure is a distinct neurological function that is linked to a complex reward and reinforcement system" (3).

The Cascade Theory of Reward

Four regions of the brain and four neurotransmitters play a significant role and are a major part of the neurological reward pathway: dopamine in the nucleus accumbens and the hippocampus; serotonin in the hypothalamus; the enkephalins in the ventral tegmental area and the nucleus accumbens; GABA - an inhibitory neurotransmitter -also in the ventral tegmental area and the nucleus accumbens (Depression Despot , - link to map of the brain's limbic system) (3). Out of all these neurotransmitters, dopamine has been singled out as "the primary neurotransmitter of reward."

In the majority of people, the reward system begins with one of these chemicals spreading out to "network" and involve the other neurotransmitters in what resembles a cascade (http://www.sigmaxi.org/amsci/captions/captions96-03/blum-4.html - link to cascade system diagram) (3). As a result, one feels "secure, calm, comfortable and satisfied," referred to as the "reward." In fact, a lot of research has shown that a significant amount of human behavior is aimed towards achieving such feelings. In its simplest definition, reward deficiency syndrome is what occurs when such "networking" does not occur (4).

Reward Deficiency Syndrome

Genetic abnormalities, exposure to a prolonged period of stress, and alcohol or other substance abuse leads to a corruption of the "cascade function" (3). Such a disruption in the interaction between the neurotransmitters results in the opposite of the "reward": feelings of anger, anxiety, and other emotions associated with negativity. It has also been linked with compulsive and impulsive disorders such as alcoholism and attention deficit hyperactivity disorder (5) (http://www.sigmaxi.org/amsci/captions/captions96-03/blum-4.html - link to table of disorders associated with reward deficiency syndrome) (3). Since dopamine has been deemed the most important of all neurotransmitters in the neurological expression of pleasure, it is a defect in the gene that carries this chemical that has been primarily blamed for the incidence of this disorder.

The D2 Dopamine-Receptor Gene

The D2 receptor has been determined the producer of the "reward"-producing neurotransmitters, and there are two main variants of the gene that contains this chemical: the A1 allele and the A2 allele (http://www.sigmaxi.org/amsci/captions/captions96-03/blum-6.html - link to diagram of gene's variants) (3). Carriers of the A1 allele are said to be predisposed to reward deficiency syndrome for the simple reason that they have about thirty percent fewer D2 receptors than carriers of the A2 allele (http://www.sigmaxi.org/amsci/captions/captions96- 03/blum-10.html - link to diagram comparing dopamine receptor numbers in an A1 allele and an A2 allele) (3). Thus, it is more likely that there are lower levels of dopamine-related activity in the brains of A1-allele carriers than in the brains of A2 carriers. And since dopamine plays a role in reducing stress as well, individuals with the A1 allele may depend on dopamine- releasing substances such as marijuana, alcohol, chocolate, and others to respond to their own stress or cravings.

The D4 Dopamine-Receptor Gene

The dopamine D2 receptor gene is thought to be the most instrumental in determining whether or not an individual will be diagnosed with reward deficiency syndrome or not; however, other genes - such as the D4 receptor gene - are believed to be involved in different expressions of the disorder. For instance, Israeli and National Institute of Mental Health scientists recently found that carriers of a certain form of the D4 gene are inclined to partake in novelty or sensation-seeking activities. The objective of their studies was to test Washington University scientist Robert Cloninger's hypothesis that such behavior is connected to the processing of dopamine. Indeed, the studies found that novelty-seekers tended to have a longer version of D4 than those who could not be classified as novelty-seekers. The latter group tended to be more calm, reflective, loyal, and rigid (3). A reason that has been offered to explain the similarity between these sensation-seekers and those with the A1 allele of the D2 dopamine receptor gene is because the D2 and D4 receptor-genes both have similar nucleotide sequences.

Are The Above Assertions Actually Valid?

The authors of the scientific articles above seem to be making the assertion that having a certain variant of either the D2 or D4 dopamine receptor gene will normally cause one to have reward deficiency syndrome. However, another notion that has been asserted before that is closer to the truth is that genes are not ever a direct cause of any such disorder. Defects in or variations of genes may distort cell functions and/or processes, which themselves may in turn cause a disorder, but the connection between genes and disorders has not yet been proven to be closer to that. Something else that raised suspicion and lessened the credibility of the claims made by Dr. Kenneth Blum and others was that the sites of those involved in the research or sites related to them were quite closely tied to those with a vested commercial interest in such a topic. For example, the "Partners For Change" website did provide some information on the syndrome; however, towards the end of the page, there was a definite emphasis on the selling of their "unique neuronutrient product" (4). It even mentions at the very end of the "article" that most of the material comes partially from the research carried out by Dr. Kenneth Blum. So while I believe that it is possible that such a syndrome does indeed exist, I cannot agree with the statement that it is directly linked to particular varieties of either the D2 or D4 dopamine-receptor gene.

. WEB REFERENCES GO IN A NUMBERED LIST AT THE END (SEE BELOW). TO CITE A WEB REFERENCE IN THE TEXT, USE THE FOLLOWING AT EACH NEEDED LOCATION: (YOUR REFERENCE NUMBER).

WWW Sources

1)Depression Despot , Clear and Basic Explanations on Depression

2)The Neurobiology of Depression (Scientific American Journal) , Neurobiological Views on Depression

3)Depression Information Center , A Clear Explanation of Depression and Facts and Figures Relation to Depression

4)Action Against Depresion (AAD) , A Page on Seeking Help for Depressed Individuals

5)Psychology Informaiton Online , Depression as a Psychological Disorder

6)Causes of Depression, A Q and A on the Causes of Depression

7)Major Depression and the Neurotransmitter Serotonin, An Explanation on Neurotransmitters [an error occurred while processing this directive]