Editor's note: Science Scan is a roundup of recently published biotechnology-related research.
Besides illicit drugs (narcotics, amphetamines, etc.), and licit drugs (nicotine, alcohol) there's another form of addiction that can wreck the life of its user, and of his or her near and dear.
Pathological gambling, because it doesn't involve any tangible substance of abuse, is called the "pure" addiction.
What it does involve is the complicity of dopamine and its receptor, which honcho major reward and pleasure centers in the brain. As such, this neurotransmitter, of which the gene resides on human chromosome 11's short arm, has at least one mutant variant that shows up particularly in abuse of hard drugs, alcoholism and other compulsive addictive behaviors.
That's why medical geneticist David Comings, at the City of Hope National Medical Center in Duarte, Calif., undertook to study the "pure" addiction from the standpoint of its genetic burden. His report, "A study of the dopamine D2 receptor gene in pathological gambling," appears in the June issue of Pharmacogenetics.
To get a clinical handle on obsessive gambling, he and his co-authors tapped two sources of information _ blood testing and in-depth questionnaires. Like smokers, Comings told BioWorld Today, most problem gamblers would like to quit, and so cooperated with the research.
The team enlisted 222 non-Hispanic Caucasian pathological gamblers from multiple sites across the U.S. Of these, 171 donated a blood sample; 127 filled out several questionnaires; 102 did both.
Genomically, the investigators looked for the presence in a subject's dopamine D2 receptor gene of a genotype variant called the TaqA1 allele. Taq is a restriction enzyme, Comings explained, which digests restriction fragment length polymorphisms of characteristic lengths.
Just as seasoned gamblers play the odds, so did the investigators. Overall, of the 171 gamblers who donated blood samples, they reported that 50.9 percent carried the D2 allele vs. only 25.9 percent of the 714 non-gambling controls, who also shunned hard-drug and alcohol excesses.
Male gamblers averaged 43.9 years of age; females, 39.7. The number of hours a week spent (some would say invested) in gambling ranged from two to 120. Of the gamblers with no drinking problems, 47.1 percent carried the D2 allele vs. 60.9 percent of those addicted to alcohol as well.
En route to full-blown addiction, obsessive gamblers advance through four stages: winning, losing, desperation, hopelessness.
To wean pathological gamblers from their games of chance, Comings said, antidepressant drugs such as bupropion are indicated; they seem to work on helping inveterate smokers quit.
`Leptinomania' Yields Three More Research Papers On Paradoxical Roles Of Weight-Regulating Protein
Since its discovery at the end of 1994, the putative anti-obesity protein, leptin, has topped the charts of follow-on research reporting. (See BioWorld Today, Dec. 1, 1994, p. 1; July 15, 1996, p. 5.)
This phenomenon has been called "leptinomania" by medical researcher George Bray, at Louisiana State University, in Baton Rouge, writing in The Lancet dated July 19, 1996.
* Its latest manifestation appears in the current issue of Nature, dated July 25, 1996, titled "Feeding inhibition by neuropeptide Y." The authors are a group in preclinical research and development at Hoffmann-La Roche Inc. in Nutley, N. J. They recall that neuropeptide Y (NPY) is a powerful appetite stimulant, and is apparently restrained by OB protein (i.e., leptin, "a circulating signal linking fat mass to the brain control of energy balance").
Leptin, they suggest, pulls off this NPY inhibition by binding to certain receptors in the brain.
From experiments with ob/ob obese mice, they conclude: "Disruption of the usual balance and interplay between OB protein, neuropeptide Y and other unidentified mediators of OB protein action seem to be important factors in the etiology of obesity and non-insulin- dependent diabetes."
* A week before, in its issue of July 20, The Lancet reported on: "Decreased cerebro-spinal-fluid [CSF] serum/leptin ratio in obesity: A possible mechanism for leptin resistance." This research by endocrinologist Robert Considine at Jefferson Medical College in Philadelphia, compared leptin levels in the blood and CSF from obese and lean individuals.
They found that leptin in the blood of obese subjects was three times that of lean, but their CSF contained only 30 percent more. They conclude that there is a limit to the rate at which leptin can travel from blood to brain, thus preventing high buildup in the CSF.
If true, this would mean that treating obesity with injections of leptin, as some have proposed, may not work.
* Leptin's main role in the body, as seen by endocrinologist Geoffrey Flier, of Boston's Beth Israel Hospital, is to keep the body on an even homeostatic keep, limiting obesity in times of abundant food; permitting fat buildup during periods of starvation.
Flier's report in Nature dated July 18, 1996, bears the title: "Role of leptin in the neuroendocrine response to fasting." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.