Cotinine

Cotinine [COAT-e-neen] is a chemical that is made by the body from nicotine, which is found in cigarette smoke. Since cotinine can be made only from nicotine, and since nicotine enters the body with cigarette smoke, cotinine measurements can show how much cigarette smoke enters your body.

Cotinine is a metabolic byproduct of nicotine. Nicotine replacement medications produce cotinine just as tobacco does.

Cotinine levels <10 ng/mL are considered to be consistent with no active smoking. Values of 10 ng/mL to 100 ng/mL are associated with light smoking or moderate passive exposure, and levels above 300 ng/mL are seen in heavy smokers - more than 20 cigarettes a day. In urine, values between 11 ng/mL and 30 ng/mL may be associated with light smoking or passive exposure, and levels in active smokers typically reach 500 ng/mL or more.

Nicotine is rapidly metabolized and has a short half-life, but cotinine is metabolized and eliminated at a much lower rate. Because of the resulting increase with time in the cotinine to nicotine ratio in the body, including in the brain, it is of interest to examine the effect of cotinine on nicotine-induced changes.

Cotinine assays provide an objective quantitative measure that is more reliable than smoking histories or counting the number of cigarettes smoked per day. Cotinine also permits the measurement of exposure to second-hand smoke (passive smoking).

Both major depression and depressive symptoms are associated with a high rate of nicotine dependence, and a history of major depression has an adverse impact on smoking cessation. The main objective of this study was to investigate whether continuous ingestion of nicotine affects indices of depressive behavior in the rat. We compared cholinergic- and serotonergic-hypersensitive Flinders Sensitive Line rats (FSL), a genetic animal model of depression, with their control counterparts, Flinders Resistant Line rats (FRL). Female rats of both lines were allowed access to a solution of nicotine bitartrate (100 microg/mL) in tap water for 14 days. Subsequent behavioral testing revealed striking effects of continuous ingestion of nicotine on depressive-like behavior of both lines. FSL and FRL rats that ingested nicotine for 14 days displayed less immobility in the 10-min forced-swim test (an index of depressive-like behavior) relative to the animals of both lines that were not exposed to nicotine or exposed to nicotine for shorter periods of time.

This finding indicates that ingested nicotine has antidepressant properties that are independent of the genetic difference between FSL and FRL female rats.

Animal studies on nicotine ingestion and withdrawal may become an important source of insights into the comorbidity of depression and nicotine self-administration.