Editor's note: Science Scan is a roundup of recently publishedbiotechnology-related research.

Besides illicit drugs (narcotics, amphetamines, etc.), and licit drugs(nicotine, alcohol) there's another form of addiction that can wreckthe life of its user, and of his or her near and dear.

Pathological gambling, because it doesn't involve any tangiblesubstance 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. Assuch, this neurotransmitter, of which the gene resides on humanchromosome 11's short arm, has at least one mutant variant thatshows up particularly in abuse of hard drugs, alcoholism and othercompulsive addictive behaviors.

That's why medical geneticist David Comings, at the City of HopeNational 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 pathologicalgambling," appears in the June issue of Pharmacogenetics.

To get a clinical handle on obsessive gambling, he and his co-authorstapped two sources of information _ blood testing and in-depthquestionnaires. Like smokers, Comings told BioWorld Today, mostproblem gamblers would like to quit, and so cooperated with theresearch.

The team enlisted 222 non-Hispanic Caucasian pathological gamblersfrom multiple sites across the U.S. Of these, 171 donated a bloodsample; 127 filled out several questionnaires; 102 did both.

Genomically, the investigators looked for the presence in a subject'sdopamine D2 receptor gene of a genotype variant called the TaqA1allele. Taq is a restriction enzyme, Comings explained, which digestsrestriction 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, theyreported that 50.9 percent carried the D2 allele vs. only 25.9 percentof the 714 non-gambling controls, who also shunned hard-drug andalcohol excesses.

Male gamblers averaged 43.9 years of age; females, 39.7. Thenumber of hours a week spent (some would say invested) in gamblingranged from two to 120. Of the gamblers with no drinking problems,47.1 percent carried the D2 allele vs. 60.9 percent of those addictedto alcohol as well.

En route to full-blown addiction, obsessive gamblers advancethrough four stages: winning, losing, desperation, hopelessness.

To wean pathological gamblers from their games of chance, Comingssaid, antidepressant drugs such as bupropion are indicated; they seemto work on helping inveterate smokers quit.

`Leptinomania' Yields Three More Research Papers On ParadoxicalRoles Of Weight-Regulating Protein

Since its discovery at the end of 1994, the putative anti-obesityprotein, 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 medicalresearcher George Bray, at Louisiana State University, in BatonRouge, writing in The Lancet dated July 19, 1996.

* Its latest manifestation appears in the current issue of Nature, datedJuly 25, 1996, titled "Feeding inhibition by neuropeptide Y." Theauthors are a group in preclinical research and development atHoffmann-La Roche Inc. in Nutley, N. J. They recall thatneuropeptide Y (NPY) is a powerful appetite stimulant, and isapparently restrained by OB protein (i.e., leptin, "a circulating signallinking fat mass to the brain control of energy balance").

Leptin, they suggest, pulls off this NPY inhibition by binding tocertain receptors in the brain.

From experiments with ob/ob obese mice, they conclude: "Disruptionof the usual balance and interplay between OB protein, neuropeptideY and other unidentified mediators of OB protein action seem to beimportant 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 byendocrinologist Robert Considine at Jefferson Medical College inPhiladelphia, compared leptin levels in the blood and CSF fromobese and lean individuals.

They found that leptin in the blood of obese subjects was three timesthat of lean, but their CSF contained only 30 percent more. Theyconclude that there is a limit to the rate at which leptin can travelfrom 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 GeoffreyFlier, of Boston's Beth Israel Hospital, is to keep the body on an evenhomeostatic 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 ofleptin in the neuroendocrine response to fasting." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.