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Addiction and the Brain

Sarah Catherine Nosal

The ponderance that Brain = Behavior and the inherent ramifications of such proves no more fascinating than when addressed in the context of "Addiction and the Brain". Essential to consider is:

-what exactly is an addictive/abusive substance (drugs of abuse)

-what brain center(s)/chemical(s)are involved

-what does it mean to become physiologically dependent

-how should the concept of addiction be addressed

-how might we use animal models

-and what sort of treatment approaches should be pursued.

These questions will be elucidated briefly, while further information remains available at the web sources listed below.

A drug of abuse/addiction would be one which leads to "recurrent and significant adverse consequences related to repeated use of the drug...[involving] compulsive drug use, interference with normal activities and may include tolerance and physical dependence" (2). The tolerance and physical dependence which frequently occurs as a normal physiological adaptation to non-addictive prescription medications must be distinguished from tolerance and physical dependence experienced in the context of addiction, a "chronic, relapsing illness characterized by compulsive drug seeking and use" ( 5).

In general, drugs of abuse tend to provoke a fast and intense change in brain chemistry, resulting in an 'intensely rewarding' euphoric state ( 1). This pleasurable state results from increased levels of the neurotransmitter dopamine (DA), a catecholamine. The elevated concentration, and increased synaptic presence of DA proves significant in the experience of pleasure, decrease of pain, and thus those components critical to the general mechanism of addiction ( 3). Those areas that release relatively large amounts of DA are the ventral tagmental area and the nucleus accumbens, the principle pleasure centers of the brain. All drugs of abuse seem to activate DA release from these two areas although each drug family tends to work via drastically different psychopharmacological mechanisms.

Besides the obvious appeal of the "high" or elation, which occurs subsequent to drug administration, a greater influence leading to an increased dosage and necessitated use, would seem the acquisition of tolerance. There are three subtypes, pharmacokinetic/dispositional tolerance, pharmacodynamic tolerance, and behavioral tolerance which all prove relevant in the drugs of abuse, with the exception of the stimulants (cocaine, methylphenidate, etc). Pharmacokinetic tolerance refers to the changes in substance distribution due to the bodies metabolism of the drug, while pharmacodynamic tolerance addresses the adaptive changes which have taken place within the system thereby reducing the efficacy of the drug. The final, behavioral tolerance, seems perhaps at once the most confusing and most compelling. Behavioral tolerance has to do with the learned tolerance in relation to a specific situation and it's environmental cues by which the body adapts and prepares itself thus minimizing the drugs effect ( 6). Thus the physiological dependence, or the need to administer the drug in order to maintain even a state of normalcy, is a direct result of these developed tolerances. It is the re-setting of the bodies homeostatic mechanisms in order to adapt for the effect of the drug which thereby necessitate its use at ever-increasing dosages ( 2). Making the substance unavailable results in the proliferation of withdrawal symptoms, which are most often experienced as the opposite of the pleasurable states initially induced by the drug.

Addressing drug abuse and addiction now becomes the relevant matter. On the whole society for the most part has chosen to brush off such abuse as a manifestation of inadequate individuals, societal structures or class standards ( 5). However, current research would indicate that, "The root of addiction is in the human brain" ( 1). As it stands this would explain why previous methods of drug control which focused on social and criminal justice aspects in an attempt to squelch drug abuse inevitably failed. Addiction, rather, must be understood as an alteration of brain format and function that results in changes that persist long after one has terminated such abuse. Dr.Leshner, Director of the National Institute on Drug Abuse, suggests that treatment strategies must include "biological, behavioral, and social context elements". Additionally, the admission of addiction as a brain disease would likely alter society's view of addiction and thereby reshape the overall approach to the treatment of affected individuals( 5).

With this biological approach, comes the search for relevant biological representations. Thankfully, Animal models prove useful in helping scientist explore the genetic and molecular basis of drug abuse and it's effect on the brain. Drosophila research has found that these flies in fact exhibit the same paradoxical sensitization response to cocaine (a "reverse tolerance" becoming more sensitive to the drug) that humans do. By investigating those mutant flies which respond atypically to cocaine further investigation of the genetic and biochemical pathways involved in the sensitization behavior may be deduced ( 4). Rats and monkeys as well are useful in that they will work to obtain injections of the same drugs which humans abuse. Manipulating their behavior, studying their abuse, and attempting treatment plans provides a framework upon which to approach the biological and behavioral aspects of drug treatment therapies.

Detoxification strategies, to eliminate drugs of abuse from the body, work best through a gradual reduction of dose - thus minimizing what may be severe and even life threatening withdrawal symptoms. Sometimes one addictive drug may be replaced by another more manageable drug, as in the case of a heroin addict put on methadone treatment. Methadone, a long-acting opioid, does not provide that sharp brain jolt that an injection of heroin provides. Rather, taken per oral it acts over a long period of time and maintains the addict in a physiologically stable state. Additionally the individual is then prompted to return to the clinic and utilize it's other counseling and support resources while continuing on the methadone treatment ( 2). This type of long term care for what may be viewed as the chronic disorder of drug addiction presents an example of the challenge and the possibility of treatment success presented in the form of illness management ( 5).

WWW Sources

1) Chapter From The Selfish Brain

2)Pharmacological Aspects of Drug Addiction

3) American Journal of Psychiatry, Editorial, "Progress in the Science of Addiction"

4) National Institute of General Medical Sciences, Fruit Flies May Shed Light on Cocaine Addiction

5) National Institutes of Justice, Addiction Is a Brain Disease - and It Matters

6) Clinical Psychology and Behavioral Neuroscience Unit, Classical conditioning and memory for drugs: Cortical and subcortical mechanisms

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This paper reflects the research and thoughts of a student at the time the paper was written for a course at Bryn Mawr College. Like other materials on Serendip, it is not intended to be "authoritative" but rather to help others further develop their own explorations. Web links were active as of the time the paper was posted but are not updated.

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