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New Insights into the Mechanisms of Action of Cotinine and its Distinctive Effects from Nicotine

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Abstract

Tobacco consumption is far higher among a number of psychiatric and neurological diseases, supporting the notion that some component(s) of tobacco may underlie the oft-reported reduction in associated symptoms during tobacco use. Popular dogma holds that this component is nicotine. However, increasing evidence support theories that cotinine, the main metabolite of nicotine, may underlie at least some of nicotine’s actions in the nervous system, apart from its adverse cardiovascular and habit forming effects. Though similarities exist, disparate and even antagonizing actions between cotinine and nicotine have been described both in terms of behavior and physiology, underscoring the need to further characterize this potentially therapeutic compound. Cotinine has been shown to be psychoactive in humans and animals, facilitating memory, cognition, executive function, and emotional responding. Furthermore, recent research shows that cotinine acts as an antidepressant and reduces cognitive-impairment associated with disease and stress-induced dysfunction. Despite these promising findings, continued focus on this potentially safe alternative to tobacco and nicotine use is lacking. Here, we review the effects of cotinine, including comparisons with nicotine, and discuss potential mechanisms of cotinine-specific actions in the central nervous system which are, to date, still being elucidated.

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Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Bay Pines VA Healthcare System. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. This work was also supported by the Bay Pines Foundation Inc. We appreciate the participation of Joyonna Gamble-George in performing experiments to investigate the effect of cotinine on fear extinction.

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Special Issue: In honor of Lynn Wecker.

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Grizzell, J.A., Echeverria, V. New Insights into the Mechanisms of Action of Cotinine and its Distinctive Effects from Nicotine. Neurochem Res 40, 2032–2046 (2015). https://doi.org/10.1007/s11064-014-1359-2

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