Nicotine’s addictive hold increases when combined with other tobacco smoke chemicals

Smoking cessation efforts could be improved by studying nicotine interactions with acetaldehyde, according to UCI tobacco use researchers

Acetaldehyde, one of the main chemical components of tobacco smoke, appears to increase the addictive properties of nicotine, according to animal studies conducted by the UC Irvine Transdisciplinary Tobacco Use Research Center (TTURC). In addition, the researchers found that adolescents are most vulnerable to the rewarding effects of the nicotine-acetaldehyde combination.

Study results appear in the online version of Neuropsychopharmacology.

Nicotine is the primary chemical in cigarette smoke that causes addiction, yet when tested in animal studies, the draw of nicotine alone appears to be relatively weak compared to other abused drugs. Surprised by this phenomenon, UCI researchers conducted a series of studies in rodents to determine whether nicotine may interact with some of the other 4,000 components of tobacco smoke to enhance addictiveness. “We chose to study acetaldehyde because it is a major component of tobacco smoke, present in a one-to-two ratio to nicotine,” said James Belluzzi, lead researcher and adjunct professor of pharmacology in the UCI College of Medicine. “Additionally, there is evidence that acetaldehyde may play a role in alcohol addiction.”

Belluzzi, researcher Ruihua Wang and Frances Leslie, professor of pharmacology and TTURC director, evaluated possible acetaldehyde and nicotine interactions in a rigorous self-administration test. Adolescent and adult male rats were tested in a procedure during which each nose poke by the rodents delivered acetaldehyde or nicotine, a combination of both drugs, or saline. Adolescent animals quickly learned to self-administer the nicotine-acetaldehyde combination significantly more than saline or either drug alone. Furthermore, young adolescents were more responsive to the drug combination than older adolescents.

When adult animals were tested in identical experiments, they did not self-administer the nicotine-acetaldehyde mixture or either drug alone at levels significantly higher than saline. Belluzzi and his team also used self-administration tests of cocaine to test the reliability of the novel self-administration procedure and to evaluate whether early adolescence was a period of enhanced vulnerability to other abused drugs. Although adolescent rats are more responsive to the nicotine-acetaldehyde mix than adult rats, the young rats were not more responsive to cocaine than adults. “Our latest findings suggest that the study of tobacco addiction, as well as the development of smoking cessation treatments, could be improved by studying the interactions of nicotine with other smoke components,” Leslie said.