When Republican presidential contender Robert Dole suggested earlier this year that nicotine in the form of tobacco was not really addictive, he set off a firestorm of controversy.

Dole defended the statement, noting that some smokers never become truly addicted to smoking. Critics pointed out that some cocaine and heroin users also continue to use those drugs without becoming hooked, but that does not mean the substances are not addictive.

Now, new research by Italian scientists published in the July 18 issue of the journal Nature reveals that nicotine shares a number of critical neuropharmacological traits with other addictive drugs such as heroin and cocaine.

"To my mind there is no doubt that nicotine should be categorized as an addictive drug," Leslie Iversen, Ph.D, of the department of pharmacology, University of Oxford, in England told Psychiatric News. Iversen wrote an accompanying commentary for Nature.

The authors "demonstrated effects on forebrain dopamine systems that were anatomically highly specific and exactly like those seen after opiates, amphetamines, or cocaine," Iversen added. Further, the effects "were elicited at very low intravenous doses of nicotine, not dissimilar to those delivered by cigarette smoking."

The study, which was conducted by Gaetano Di Chiara of the department of toxicology and CNR Center for Neuropharmacology at the University of Cagliari in Italy, and colleagues, measured the neurophysiological response of rats to intravenous doses of nicotine.

Rats, of course, cannot be taught to smoke. But scientists reasoned that the physiological dynamics of an i.v. dose are similar to those of smoking in that the drug goes almost instantly to the brain either way.

The capacity to increase selectively dopamine transmission and glucose metabolism in the shell of the brain's nucleus accumbens is characteristic of addictive drugs. Last year, Di Chiara and his colleagues reported that cocaine, amphetamine, and morphine stimulated a selective release of dopamine from the shell region of the nucleus accumbens in the rat brain. The current study reveals that nicotine shares that functional capacity.

That dopamine is critical in mediating rewarding behavior is clear, the authors note. Increased dopamine transmission in the shell of the nucleus accumbens "might induce positive motivational states" leading to incentives to self-administer tobacco, and ultimately, to compulsive use, they speculate. The role of the shell region in the rat brain may be to link midbrain and forebrain, thereby tying together motivational and emotional functions, Iversen suggested.

In the accompanying commentary, Iversen notes that "for centuries after its introduction" tobacco was regarded as a benign self-indulgence. Beginning in the 1950's, evidence that it was harmful accrued, and by the 1980's, evidence that it was addictive grew increasingly persuasive.

Iversen suggests that King James I of England, in 1604, may have anticipated modern research findings when he wrote:

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.

(Psychiatric News, September 6, 1996)