Who wrote these words of warning?

Tobacco is a filthy weed.

That from the devil does proceed;

It drains your purse; it burns your clothes,

And makes a chimney of your nose.

No, it was not U.S. Surgeon General C. Everett Koop but a muchearlier American physician, Benjamin Waterhouse (1754-1846), whopioneered smallpox vaccination in the U.S., and co-founded HarvardMedical School in 1783. Koop published his famous declaration in1988 on The Health Consequences of Smoking and NicotineAddiction.

Now, try this one:

A custom loathsome to the eye,

harmful to the nose, harmful to the brain,

dangerous to the lungs,

and in the black stinking fume thereof,

nearest resembling the horrible Stygian smoke

of the pit that is bottomless.

None other than King James I of England penned this pronouncementfour centuries before Koop, in 1604 A.D.

His royal rescript has just resurfaced in today's Nature, quoted by thenoted British neuropharmacologist Leslie Iversen, of OxfordUniversity. Iversen's 1604 citation concludes his commentary on apaper in Nature titled: "Effects of nicotine on the nucleus accumbensand similarity to those of addictive drugs."

Its senior author, neuropharmacologist Gaetano Di Chiara, heads agroup at Italy's University of Cagliari, Sardinia, which has pioneeredstudies of nicotine's effects in the brain for over a decade.

In 1988, Di Chiara and his colleagues were able to show that avariety of illicit drugs of abuse, plus ethanol and nicotine, hadsomething in common: They all triggered release of the dopamineneurotransmitter in the brain's nucleus accumbens.

"The form of that dopamine-release spike," Alan Leshner, director ofthe National Institute on Drug Abuse (NIDA), told BioWorld Today,"is similar to the form of the spike in cocaine. But, I would not take itfurther than that."

NIDA Chief Deems Nicotine Addictive

Leshner did make the point that thanks to such findings, "We arebeginning to get insights into the addictiveness of drugs, rather thanjust how a particular drug works."

Is nicotine, then, addictive?

"There are 500 different uses for the term, `addicting,'" Leshnerobserved. "I am interested only in the clinical definition, which is`compulsive, uncontrollable drug use.' There is no question but thatnicotine meets this criterion."

NIDA's director continued: "The next critical point is thatcompulsive drug use correlates with increases in dopamine levels. Sothat the clinical condition _ which is all anybody cares about really_ is tied to the brain mechanism of addiction. The next obviousquestion is: `What would we treat?' _ and I don't know. We have notyet found a treatment for any addiction by manipulating dopaminelevels alone."

Behavioral neuroscientist David Self, at Yale University, suggestedon this point: "What really needs to be done is more research on thepharmacology of nicotine receptors, which activate the dopaminesystem. This may open up avenues for therapeutic intervention _beyond nicotine skin patches and chewing gum.

"Those looking for treatments for nicotine addiction are basicallyusing a form of replacement therapy that may be similar to whatwe've done with the dopamine agonist against cocaine addiction,"Self said. (See BioWorld Today, March 16, 1996, p. 1.)

Tackling the zillion-dollar A-question, Self suggested, "In terms ofdrug dependence _ the psychiatric synonym for addiction _ nicotineisn't disruptive of life style, but it is addictive, in that people can'tgive it up. It's all semantic."

Oxford's Iversen cited "the high relapse rate in smokers who attemptto stop (more than 95 percent within 12 months, similar to the rate forheroin addicts)."

Di Chiara and his co-authors reported today in Nature that"intravenous nicotine, at doses known to stimulate self-administration, stimulates . . . dopamine transmission . . . in the shellof the nucleus accumbens [Nac]," which is currently recognized asthe dart-board target for drugs of abuse.

They divided this Nac bull's eye into two sub-targets, a "shell" and a"core", one presumed to be involved in emotions, the other insomato-motor functions.

Nicotine Joins Hard Drugs On Cerebral Dart-Board

Last year, the Cagliari group showed in rats that cocaine,amphetamine and morphine, all strongly addictive, increaseddopamine levels in the Nac shell. Their present paper adds nicotine tothat list.

They injected the substance by catheter into the veins of anesthetizedlaboratory rats at two different doses. Within minutes of awakening,the animals showed arousal by sniffing the air and stepping up theirmovements around their cages.

"The intravenous bolus of nicotine," the paper observed, "veryclosely approximated the pharmacokinetics of nicotine inhaled intobacco smoke."

Finally, the team prepared brain sections, and micro-measured thelocal energy metabolism, and dopamine release, in some 40 limbic,sensory and motor brain structures. The Nac shell showed increasedactivity over the region's core. Other brain regions reacted little ornot at all. n

-- David N. Leff Science Editor

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

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