Positron emission tomography (PET) is helping researchers determine if a connection exists between dopamine levels in the brain and the risk of alcoholism within a family, or the threat of relapse for a detoxified alcoholic.
To examine this relationship, two studies have focused on the striatum part of the brain, which includes the caudate and the adjacent putamen, or lower section of the striatum. The striatum is involved in the brain's cognitive processes, such as planning and thinking, and responds to stimuli associated with reward, as well as aversive, unexpected, or intense stimuli.
Dopamine's protective effect
The most recent study was published in the September issue of the Archives of General Psychiatry. Researchers affiliated with the Brookhaven National Laboratory in Upton, NY, and led by Dr. Nora Volkow, director of the National Institute on Drug Abuse (NIDA) at the National Institutes of Health in Maryland, sought to determine the role dopamine D2 receptors play in alcoholism (September 2006, Vol. 63:9, pp. 999-1008).
The team evaluated 15 people whose biological fathers had a history of alcoholism and who had some history of alcoholism with one or two other close relatives, designated the family-positive (FP) group. To compare the possible influence of dopamine receptors, the analysis included 16 people with no family history of alcoholism or drug abuse, designated the family-negative (FN) group.
The researchers used an ECAT Exact HR+ PET system (Siemens Medical Solutions, Malvern, PA) to gather images in 3D dynamic acquisition mode, scanning 31 subjects after injections of either nonradioactive raclopride or fluorodeoxyglucose (FDG). Twenty images were obtained for as long as 54 minutes after the injection of raclopride. With FDG, a 20-minute scan was started 35 minutes after injection.
After PET scanning and analysis of the results, the researchers found that high D2 receptor levels exert a "protective effect" against alcoholism. The "significantly higher D2 receptor availability in the caudate and in ventral striatum in the FP group compared with the FN group corroborates our working hypothesis that a high D2 receptor level in striatum is a protective factor against alcohol abuse," they added.
Also, despite a family history of alcoholism, "nonalcoholic members of alcoholic families may be enriched with protective factors, including high D2 receptor availability, that compensate for the higher inherited vulnerability," they stated.
Alcoholic cravings
In a 2005 study published in the American Journal of Psychiatry (August 2005, Vol. 162:8, pp. 1515-1520), PET also was used to compare dopamine synthesis capacity in the striatum in alcoholic patients and healthy volunteers to determine the role that low availability of dopamine D2 and D3 receptors may play in someone's craving of or addiction to alcohol.
The study, by researchers from the Central Institute of Mental Health in Mannheim, Germany, and supported by a grant from the German Research Foundation, began with the hypothesis that low levels of dopamine D2 and D3 receptors in the striatum and putamen would prompt a strong desire for alcohol.
The German group also utilized a Siemens ECAT Exact PET scanner to image 12 male alcoholic patients and 13 nonalcoholic volunteers over five days. The PET scans were used to measure and analyze the increase in benzamide radioligand, which binds to D2 and D3 dopamine receptors.
The process began with the hypothesis that the net influx of dopa decarboxylase substrate F-18 fluoro-L-dopa (F-18 DOPA) to the striatum is lower in alcoholic patients than in the healthy group of volunteers. The researchers found that while there was no difference between F-18 DOPA levels of either group, the "severity of alcohol craving was significantly and negatively correlated with F-18 DOPA net influx in the bilateral putamen."
What additional light the study may shine on the chance that a detoxified alcoholic will relapse "remains a topic for debate," the researchers stated. While alcohol craving was "significantly and positively correlated" with the amount of alcohol consumed during a six-month follow-up period, "no significant correlations were found between subsequent alcohol intake and the severity of alcoholism."
By Wayne Forrest
AuntMinnie.com staff writer
October 5, 2005
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