Examining the Neuroprotective Effects of Nicotine

Examining the Neuroprotective Effects of Nicotine

by

Ainsley MacDougall

201102169

A laboratory report

presented to Dr. Brebner

in Psychology 368

Psychopharmacology of Drugs of Abuse

Department of Psychology

St. Francis Xavier University

March 19, 2015

Nicotine, a drug with a wide range of effects, is principally known as the psychoactive chemical in tobacco (Rezvani & Levin, 2001). Originating in the Americas, tobacco was first administered by aboriginal peoples. Historically, the primary means of administering tobacco was through smoking, and recreational smoking remained popular until the 1960’s, when it was found to be associated with cancer (McKim & Hancock, 2013). Since that time, prevalence of smoking has decreased and nicotine has not only been found to be acutely toxic, but also has been linked to many other serious health consequences such as heart disease, fertility problems, type II diabetes, and respiratory diseases (U.S. Department of Health and Human Services, 2014).  Recent research, however, has suggested that nicotine produced neuroprotective effects in both animal and human models, and smokers have been shown to be less likely to develop certain diseases. In exploring the ways nicotine produces such effects and examining the specific conditions on which it has therapeutic potential, the following literature acts to provide evidence that discovering safe and effective ways to use nicotine could be beneficial for patients suffering from neurodegenerative diseases.

Regardless of the route of administration, nicotine in its unionized state can easily enter the body (U.S. Department of Health and Human Services, 2014). According to McKim & Hancock (2013), 90% of nicotine is absorbed through the burning of the drug, which then vaporizes and is carried to the lungs in the form of smoke. Cigarettes, the most popular form of inhaling tobacco smoke, deliver varying amounts of nicotine to a user; with the volume of smoke inhaled being the major determinant of how much nicotine is subsequently absorbed. Along with mucous membranes, buccal membranes in the mouth also act to absorb nicotine and are the major route of administration for cigars and pipes. Upon entering the blood, nicotine circulates to the brain where it remains for about 30 minutes before circulating into some organs and the salivary glands. Nicotine has a short half-life (McKim & Hancock, 2013), and around 80% of the metabolism occurs through enzymes in the liver (The U.S. Department of Health and Human Services, 2014).

Nicotine spreads a wide array of effects throughout both the central and peripheral nervous systems (McKim & Hancock, 2013). West (1993) listed the effects of nicotine that could be observed in users, which included a feeling of light-headedness, tremors, nausea after initial administrations, and accelerated heart rate. Although smokers viewed cigarettes as being beneficial to their lives, it was found that in comparison to non-smokers and previous smokers, those who currently smoked had lower levels of psychological well-being (West, 1993). Smoking was also perceived to be a stress reliever, but the U.S. Department of Health and Human Services (2014) reported that it actually increases physical stress by activating the parasympathetic system.

        Markou (2008) reported nicotine dependence as being more common than any other form of substance dependence. Murray & Lopez stated that the prevalence of nicotine dependence had lead to high mortality rates internationally (as cited in Markou, 2008). Immediate nicotine exposure produced rewarding effects, such as slight euphoria and increased cognition. Animal models have mirrored such results, and withdrawal symptoms, such as fatigue and anxiety, have also been shown to be analogous in humans and animals. After reviewing evidence, Markou (2008) concluded that interactions between neurotransmitters such as acetylcholine, glutamate, GABA, and dopamine in the limbic system structures have important implications in initial the initial feelings of reward produced by nicotine.  

        Despite nicotine being an important contributor in the abuse of tobacco, it also has effects that are potentially useful for therapeutic purposes (Rezvani & Levin, 2001). Brain systems associated with nicotine are imperative in functions such as memory, attention, and certain mental disorders. Previous research had suggested that treatment through nicotine administration could increase cognitive function in a variety of patients, including adults that do not smoke, persons diagnosed with Alzheimer’s disease, and adults with learning disabilities such as ADHD. The primary cognitive effects of nicotine could be observed through its ability to improve memory, and such effects had not been shown to decrease after chronic nicotine use. Rezvani & Levin (2001) reported that, in alignment with previous findings, nicotine and its compounds could be protective in treating cognitive deficits that appear with Alzheimer’s disease, ADHD, and schizophrenia.

        Nakamura, Takahashi, Yamashita, and Kawakami (2001) conducted research on nicotinic acetylcholine receptors (nAChRs) and suggested nicotine produced its neuroprotective effects through these receptors. Due to interactions at nAChR sites, nicotine has been found to stimulate the release of many neurotransmitters in the brain (U.S. Department of Health and Human Services, 2014). Nakamura et al. (2001) stated previous research found nAChRs in the central nervous system to show potential for protective effects. These effects have been suggested to occur through the binding of nicotine to nAChRs, which might prevent dopamine uptake. In examining Alzheimer’s disease specifically, Nakamura et al. (2001) reported that the expression of the beta-amyloid precursor protein (APP) was considered to be a major event in the development of the disease. Administration of nicotine for a period of ten days was found to lower the expression of APP in experimental rats, which suggested that nicotine produced inhibitory effects on the synthesis of APP itself. Further observations implicated the important role of nAChRs when Nakamura et al. (2001) reported that the protective effects of nicotine were not seen when a nAChR antagonist drug was tested on the experimental rats. Nakamura et al. (2001) concluded that based on the cognitive and neuroprotective effects that nAChRs produced, such receptors were required to produce potentially therapeutic effects in both Alzheimer’s and Parkinson’s disease.

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