Neurochemical Systems Used To Study Brain and Behavior

Theoretically, it should someday be possible to reverse the effects of brain chemistry changes brought on by addiction. However, no technique has yet been found that can do that. At Brookhaven National Laboratory, an interdisciplinary team of 20 researchers from the Medical and Chemistry Departments is investigating how neurochemical systems affect both brain and behavior. Cosponsored by DOE and the National Institutes of Health (NIH), the team uses positron emission tomography (PET) imaging and neuropsychiatric measures to observe and correlate brain chemistry with addictive behaviors. The researchers hope this therapeutic intervention can eventually be tailored to treat specific stages of addiction.

Led by psychiatrist Nora D. Volkow and chemist Joanna S. Fowler, the Brookhaven team has been studying the activity of the brain’s dopamine system by “stressing” the brain with a psychostimulant, such as methylphenidate, and then using a labeled tracer and PET scan to track the accumulation of dopamine in the brain. By correlating the dopamine activity with the behavioral and genetic characteristics of a subject, they hope to build biological and psychological profiles of addiction.

This interdisciplinary approach may lead to better treatment for those suffering from addiction. To determine what the effects of a drug are, it is necessary both to observe the drug acting in the brain and to ask the persons affected what they are experiencing. This is possible with PET because studies are carried out when the subject is awake. A multidisciplinary approach holds promise because brain chemistry is so complicated. Neurotransmitters are known to work collaboratively, producing a sort of constellation effect that involves brain chemistry, symptoms, and behavior.

Influx constant images for a nonsmoker; a smoker; and a subject who had received L-deprenyl, a MAO B inhibitor, for 1 week. The same four planes left to right are 4.7, 3.5, 2.8, and 1.4 cm superior to the canthomeatal line and show the thalamus, basal ganglia, ventral striatum, and cerebellum for each subject. The color scale is shown with red corresponding to Ki=0.3 cubic cm brain per ml plasma per min. The Ki values for the thalamus are 0.29 for the nonsmoker, 0.11 for the smoker, and 0.017 for the subject who received L-deprenyl.

Dependence on alcohol, opiates, cigarettes, or cocaine relies on a set of biochemical mechanisms that have the same end result: the release of a neurotransmitter (a “messenger” substance) called dopamine, which produces feelings of satisfaction and reward. Past research has led to the conclusion that successful treatment of addiction requires a better understanding of how addictive substances affect the brain.

Recent studies by the Brookhaven team revealed that something about cigarette smoking creates a synergistic effect that enhances the brain’s dopamine activity. Cigarette smokers have lower levels of monoamine oxidase B (MAO B), an enzyme that breaks down dopamine. In fact, smokers experience a surge of dopamine, apparently brought on by the nicotine in the smoke. Moreover, some other substance (thus far unidentified) also prevents the breakdown of dopamine in the brain, allowing it to accumulate in the brain’s reward center, the nucleus accumbens. Although the chemical component of smoke that inhibits the action of MAO B is unknown, it has been determined that it is not nicotine. In an article in Nature (22 February 1996), Fowler, Volkow, and others suggest that “MAO B inhibitor drugs may be useful as an adjunct in smoking cessation.”

The Brookhaven team is continuing to investigate how addictive substances, such as cocaine, alcohol, and tobacco smoke, affect brain chemistry and behavior. Addictions are probably long-term changes in brain chemistry. Nevertheless, the studies at Brookhaven suggest there are time phases in the addictive process–that brain chemistry changes are different at different times. Identifying the stages of addiction may be a fundamental element in designing interventions for a specific stage of addiction.

The work of Volkow and Fowler and the Brookhaven team is supported by the DOE Office of Health and Environmental Research and by the National Institute of Drug Abuse and the National Institute on Neurological Diseases and Stroke (both part of the National Institutes of Health). (Contact: Joanna Fowler, Brookhaven National Laboratory, 516-344-4365, e-mail: fowler@bnl.gov)

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