Investigations into the cognitive effects of tobacco smoking have generally focused on nicotine and its effect on nicotinic acetylcholine receptors (nAChRs) in the brain. However, it is now known that chronic smokers exhibit robust inhibition of the monoamine oxidase (MAO) enzyme through the actions of non-nicotine components in tobacco smoke. Therefore, the primary aim of this thesis is to elucidate the effects of nicotine and MAO-inhibition on electroencephalographic (EEG) and event-related potential (ERP) measures of cognition. 24 healthy nonsmoking males were administered 75 mg of moclobemide, and chewed 6 mg nicotine gum, in order to simulate the effects of acute smoking. Four experimental conditions included placebo, nicotine, moclobemide, and a combination of nicotine and moclobemide. Early auditory ERPs were used as measures of cognition, such as the auditory P50 sensory gating paired-stimulus paradigm, the acoustic-change-elicited mismatch-negativity (MMN), the novel sound-elicited P3a, and the target sound-elicited P3b. Three minutes of eyes closed EEG were also recorded. Because these ERPs are often identified as biomarkers for schizophrenia, drug effects were also measured after individuals were stratified for low-baseline amplitude of each ERP measure, as a laboratory model of cognitive deficits in schizophrenia. Overall results showed a synergistic improvement in sensory gating via nicotine combined with moclobemide, accompanied by a reduction in theta band power. Nicotine in the absence of moclobemide increased P3b amplitude, accompanied by an increase in alpha2 band power. Moclobemide in the absence of nicotine increased P3a amplitude, accompanied by a decrease in beta2 power. Stratifying participants by placebo amplitude revealed both nicotine and moclobemide exhibited an inverted-U pattern of effect, i.e. showing greater amplitude increases in individuals with the lowest baseline amplitudes. Overall, this thesis demonstrates how these two components of tobacco smoke affect different facets of auditory processing in different ways, with synergistic effects in some paradigms but antagonizing effects in others. Therefore, chronic smokers and schizophrenia patients who seek transient cognitive improvement through smoking may actually experience cognitive detriments overall, possibly contributing to withdrawal symptoms and/or an exacerbation of already-present psychiatric symptoms.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/33418 |
| Date | January 2015 |
| Creators | Smith, Dylan |
| Contributors | Knott, Verner |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0021 seconds