Date of Award

6-15-2017

Document Type

Closed Thesis

Department

Psychology

First Advisor

Matthew M. Ford

Subjects

Cellular signal transduction, Stress (Physiology), Substance abuse -- Physiological effect, Tobacco -- Physiological effect

DOI

10.15760/honors.494

Abstract

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.

Comments

An undergraduate honors thesis submitted in partial fulfillment of the requirements for the degree of Bachelor of Arts in Psychology

Persistent Identifier

http://archives.pdx.edu/ds/psu/23045

Share

COinS