Matthew M. Ford
Date of Award
Bachelor of Arts (B.A.) in Psychology and University Honors
Tobacco -- Physiological effect, Alcohol -- Physiological effect, Mice -- Effect of drugs on -- Case studies, Neuropsychopharmacology
The use and abuse of alcohol and nicotine are intimately related, with co-use of alcohol among adult cigarette smokers higher (>65%) than non-smokers (>45%), and smoking rates among alcoholics above 75%. Smoking is associated with an accelerated progression to alcohol dependence, suggesting that nicotine and alcohol act in a synergistic manner to promote co-abuse. While recent work has begun to identify discrete ‘neuronal ensembles’ within stress and reward circuitry components that underlie nicotine’s contribution to escalations in alcohol self-administration, the neurobiological mechanisms facilitating alcohol-nicotine interactions following chronic drug exposure remain understudied. The goal of the current work was to identify a network of brain regions in mice that are activated differentially following chronic intermittent exposure to alcohol versus alcohol plus nicotine combinations via c-Fos immunoreactivity. Male C57BL/6J mice were systemically treated with either alcohol (1.5 g/kg) or a combination of alcohol plus nicotine (0.4, 0.8, or 1.2 mg/kg base) on a double-alternation schedule (drug, drug, saline, saline) for a 13-month period. Mice were euthanized 90-min following the final treatment, whole brains were removed and 40-µm coronal sections were evaluated for c-Fos immunoreactivity using established laboratory procedures. Co-administration of 0.4 and 0.8 mg/kg nicotine dose-dependently enhanced c-Fos immunoreactivity in the ventral tegmental area (VTA), centrally projecting Edinger-Westphal nucleus (cpEW), and the lateral septum (LS) when compared to alcohol only treated mice. In contrast, co-administration of 1.2 mg/kg resulted in a 33% decline in c-Fos labeled cells within the VTA, no change in LS activation, and comparable activation to 0.4 mg/kg nicotine in the cpEW. In summary, chronic intermittent nicotine exposure exacerbates the c-Fos response to alcohol in a dose-dependent and brain region-selective fashion. The nearly uniform, maximal response observed following 0.8 mg/kg nicotine across stress- and reward-associated brain regions is consistent with the ability of this dose to accelerate the progression towards excessive alcohol self-administration and to potentiate the discriminative stimulus effects of alcohol in rodents.
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Schoen, Jacob J., "Ethanol-Nicotine Combinations Induces C-Fos Expression within Stress and Reward-Related Circuitry" (2017). University Honors Theses. Paper 491.