Biology 202
2000 Third Web Report
On Serendip

One of the central questions surrounding the study of addiction is discerning why people choose to use the drugs that they do. In studies of both people and animals, the subjects have shown compulsive tendencies, characteristic of addiction, in respons to compounds that fulfill three properties. They act on the central nervous system, they central nervous system effects occur rapidly, and there is a withdrawl period after continued use is stopped ((2)).

Alan Leshner, director of the National Institute on Drug Abuse (NIDA) gives two reasons that people use drugs. First they use them to feel good (sensation seeking), and then they use them to feel better (self-medicating). An addict will move quickly from the voluntary period of drug use to compulsive behavior motivated by craving. Addiction is defined as having both physical and psychological components. Physical components include tolerance and signs of withdrawl when use is stopped. Psychological components are compulsive drug seeking and use, loss of control over use, and continued use despite negative physical and social consequences. Dependence upon a substance or behavior includes the psycological aspects of addiction, but not the physical addiction ((6)).

Scientists have traced the neurobiological foundations of addiction to the ventral tegmental area (VTA) where the reward circuit is located. The reward system in the brain is activated when a person performs an action necessary to survival, such as eating. Activation of the reward circuit provides pleasurable feelings, giving positive feedback for necessary actions. Most abused drugs stimulate the reward system, and often provide greater pleasure than is normally the result of natural stimulation. The reward system underlies addiction to cocaine, speed, angel dust, herione, morphine, alcohol and tobacco ((4)).

Many drugs cause physical addiction by affecting the levels of neurotransmitters, specifically dopamine and glutamate, in the reward circuit of the VTA. Specifically, cocane and amphetamine are known to act by changing the flow of neurotransmitters coming into receptor cells. Cocaine prevents dopamine reuptake, while amphetamine cause the amount of dopamine released into a the synapse to increase. Both of these mechanisms increase the dopamine concentration of the synapse, causing pleasurable feelings greater than what can normally be obtained naturally ((1)). It has always been thought that dopamine was the key neurotransmitter involved in addiction. However, recent studies have shown that glutamate may play as large, or even possibly a larger role than dopamine does. Recent studies have shown the brain structures rich in glutamate are involved in learning processes which play a part in developing drug cravings, one of the central aspects of compulsive drug seeking and use.

With repeated use, drugs affecting the reward system will cause tolerance ((3)). A negative feedback loop exists in the synapses of the reward system to keep the neurotransmitter concentration around a certain set value. When a neuroactive compound is taken, the neurotransmitter concentration is shifted, and the so the neurons react, either producing more or less neurotransmitter to keep the concentration around the established set point. However, over an extended period of time, intense use of the same drug can shift the set point on a semipermanent basis. Over time, it takes a larger dose to achieve the same effect. This phenomenon is known as tolerance, and is a key part of diagnosing addiction ((1)).

Following directly from tolerance is the second physical indication of addiction, withdrawl, also known as a rebound response. Addiction is a chronic and relapsing disease which causes physical changes in the brain ((8)). The brain of an addict is different in metabolism, receptor availability, gene expression, and responsiveness to environmental cues ((6)). Addicting drugs can induce long-term changes in teh morphology of the brain ((8)). For example, the dopamine-using neurons of the VTA are much smaller in the brains of addicts then in non-addicted brains. Over a decade ago, the self-medicating hypothesis of drug addiction was proposed. This hypothesis states that "Individuals discover that the specific actions or effects of each class of drugs relieve or change a range of painful side effects." According to this theory, addicts do not use drugs to receive pleasure, but rather to fend off the adverse effects of not using. Once chronic drug use has shifted the equilibrium in the brain on a long-term basis, the person becomes dependent upon the drug to maintain a normal lifestyle. When the drug is removed from the system, the body does not rebound to the homeostasis that existed before addiction for days or weeks, and in this time, the person can feel a great degree of discomfort. For example, alcohol is a central nervous system depressent, which with chronic use stimulates the CNS to produce more excitatory neurons to combat the effects of the alcohol. When alcohol use stops, neurotransmitter production continues at it's elevated levels, causing the person to be anxious, and at times to visibly shake ((4)).

Once the foundations of understanding addiction have been layed, the next obvious question is how to treat it. The mechanisms of addiction formation operate for the most part with out any influence upon or from the "I" function. However, the "I" function plays a quintesential role in treating addiction. The only cure for physical addiction is time. With time, the equilibrium point for the neurotransmitters of the reward circuit will return to their pre-addiction levels. In some cases, as in the case of herion, withdrawl effects can be so dangerous that the addict must take methadone, which helps to curve the craving for herion, and helps to lessen rebound response. However, it is also necessary to overcome the psychological aspects of addiction. One of the key ways in which the psychological aspects are confronted is through changing the behaviors associated with ingesting the drug. For instance, smokers who are trying to quit often find some other form of obtaining nicotine without actually smoking, thus breaking the psychological link between the behavior of smoking and the stimulation of the reward circuit ((8)).

The reward circuit, located in the ventral tangental area of the cortex, plays a central role in the neurobiology of addiction. It has only been in the past few years that addiction has been recongnized as a disease that does require treatment rather than as a lack of will power. While the mechanisms of addiction lie for the most part outside of the bounds of human conciousness, the "I" function, the concious part of the brain, is responsible for overcoming the forces of addiction before they overcome the whole body.

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WWW Sources

2) Tolerance, Drug Abuse and Habitual Behaviors

3)About Addiction

4) Addiction's Path

5) The Opiate Receptor

6) Brainstorm: Exploring the Body, Mind and Soul of Addiction, Part 1

7) Brainstorm: Exploring the Body, Mind and Soul of Addiction, Part 2

8) Moyers on Addiction

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