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“Smoking is the leading cause of statistics”
– Fletcher Knebel

A study published in Brain Sciences found that non-nicotine elements in cigarettes combine with nicotine to have a stronger addictive effect together than nicotine alone, and that, together, these compounds cause changes in the underlying brain activity of the reward system. 

This research was conducted by Jieun Kim, Ju Hwan Yang, Sumin Sohn, Sunghyun Kim and Eun Sang Choe at the Pusan National University in Korea, as well as In Soo Ryu, Kyuhong Lee and Joung-Wook Seo at the Korea Toxicology Institute and Su Yeon Seo at the Korea Institute of Oriental Medicine. 

It has long been known that nicotine is addictive. However, cigarette smoke is composed of a mixture of both nicotine and non-nicotine compounds. The non-nicotine compounds are similar in their chemical structure to nicotine in that they can both lead to similar dependencies

When these compounds are inhaled through the lungs they can travel through the circulatory system to the brain. Once in the brain, nicotine and non-nicotine compounds bind to brain cells via receptors and cause a chain of signals to be passed from one brain cell to the next.

The brain has a natural state in which certain compounds bind to specific receptors in particular brain regions. Since cigarette smoke is not a natural compound, it causes changes to occur to the natural state of the brain. Previous research has documented that dependencies form from the use of cigarettes via the brain’s reward system. Cigarette dependency, in turn, causes a change in behavior by affecting the motivational influences on one’s physical actions. 

It has been previously well-documented that nicotine is the addictive compound in cigarette smoke. However, rarely are all compounds in cigarette smoke evaluated for their synergistic addictive properties. The purpose of the current study was to determine the motivational changes in behavioural activities and the brain changes in rats associated with different combinations of compounds found in cigarette smoke.

The researchers hypothesized that nicotine and non-nicotine compounds together would have a stronger effect on brain receptors and subsequent psychomotor behaviors than would either compound, individually.\

Study and findings

To conduct the study, the researchers chose 48 different rats based on weight (200g-230g). Once the rats were acclimatized to their cages, they were divided into two different groups where they would be tested for either behavioral activity changes (n = 24) or brain activity changes (n = 24). Half the rats in each group received an injection of nicotine alone, non-nicotine, and then nicotine compounds, while the other half just received the vehicle that each compound was diluted into (control group).

The behavioural experimental groups were administered (via injection) one of four options: nicotine alone, one of two different brands of cigarette smoke (containing both nicotine and non-nicotine chemicals), or the control. All rats were kept on a strict administration regime of one injection per day. Administration began with 14 days of injection, followed by six days of withdrawal (no injection) and ending with 14 more days of respective injections. 

Rats in the experiment that were measured for psychomotor activity changes were put through a behavioral test assessing total distance travelled, how often they stood on their hind limbs (rearing) and number of rotations physically completed to observe abnormal motor activity associated with psychoactive substances. 

The twenty-four rats in the neural-activity group underwent surgery to implant a sensor that detects when compounds bind to receptors of interest in the area of the brain that is associated with the reward system (dorsal striatum). After surgery, the rats were given six days to recover.

After recovery, the neural-activity rats were divided into four groups of six: for the 14 days of injections, one group received control injections, another received nicotine, and each of the final two groups received one of the two brands of cigarettes’ smoke. After the last administration of their respective injection, the sensor was turned on for one hour and the rats were free to move around in their home cages.

The researchers found both behavioral and neurological support for their hypotheses. Behaviorally, the rats exposed to both brands of cigarette smoke demonstrated and sustained more ambulatory, rearing, and rotational activities than did those exposed to just nicotine or the control. At the neurological level, repeated exposure to either of the two brands of cigarette smoke resulted in higher concentrations of glutamate in the brain’s reward center (the dorsal striatum) than did nicotine alone.

Furthermore, the increases in psychomotor behaviour caused by the cigarette smoke were highly correlated with glutamate concentrations in the dorsal striatum.

Adding to our current understanding of addiction, When a person smokes a cigarette, the different compounds it contains work synergistically to cause changes in the activity in their brain’s reward system, leading to stronger motivational influences and having a more pronounced effect on behavior than nicotine alone.

 
Nick Hobson