LOS ANGELES—It may someday be possible to help smokers kick the habit with dopamine agonists, says Nicholas H. Caskey, PhD, staff psychologist at the VA Greater Los Angeles Healthcare System. Dr. Caskey and coworkers found that smoking behavior was significantly lower among heavy smokers after administration of the dopamine agonist bromocriptine than it was with haloperidol, a dopamine antagonist.[1]

These findings replicate the results of previous experiments by Dr. Caskey’s group in which the effects of bromocriptine and haloperidol on smoking behavior were separately assessed. The study findings also support the hypothesis that the nicotine in cigarettes fosters smoking by triggering dopamine release in reward areas of the brain.

BEHAVIOR MANIPULATION IN OPPOSITE DIRECTIONS

“Our study’s lack of placebo control may be viewed by some as an important design flaw,” said Dr. Caskey in a recent interview. “But we did not have a placebo group because one was included in earlier experiments in which the effects of the two drugs on smoking were examined separately.”

The investigators were therefore satisfied to compare bromocriptine and haloperidol in the current study to see if they could manipulate smoking behavior in opposite directions. Subjects consisted of 20 heavy smokers with a mean age of 30. These subjects had smoked for an average of 12.5 years and were smoking an average of 20.1 cigarettes daily at the time of the study.

Participants received either 2.5 mg of bromocriptine or 2.0 mg of haloperidol on two separate occasions one week apart. After drug administration, their smoking behavior was observed for a five- to six-hour period during which they were permitted to smoke freely.

Data were collected with an electronic timer and a thermistor embedded in a cigarette holder. These devices enabled the investigators to measure six aspects of smoking behavior—when a cigarette was started and finished, puff duration, the number of puffs per cigarette, and the intervals between puffs and between cigarettes.

INCREASED SMOKING WITH HALOPERIDOL

The subjects took more puffs, smoked more cigarettes, and had a higher total puffing time when haloperidol was given than when bromocriptine was used. Their mean puff duration was nearly identical with the two drugs, however. The interval between cigarettes was also shorter with haloperidol, although this difference did not meet statistical significance.

Smoking invariably caused the subjects’ blood level of the nicotine metabolite cotinine to rise. Although the increase persisted with haloperidol, it fell off after several hours when bromocriptine was given. A similar but nonsignificant pattern was observed for the carbon monoxide concentration in subjects’ breath samples. The subjects also reported significantly more cravings with haloperidol.

NAUSEA NOT THE EXPLANATION

“Some people might attribute the differences in smoking behavior we found with these two drugs to nausea, which was more common with bromocriptine,” Dr. Caskey acknowledged. However, he added. “Our analysis showed a substantial drug effect independent of nausea.”

If dopamine agonist therapy were eventually adopted for smoking cessation, a drug other than bromocriptine would probably have to be used, Dr. Caskey speculated, because of its tendency to induce nausea.

—Timothy Begany