THE FUNCTIONAL CONNECTIVITY CHANGES IN THE RAT BRAIN FOLLOWING ACUTE AND CHRONIC NICOTINE ADMINISTRATION

Open Access
Author:
Roby, Alison C
Area of Honors:
Biomedical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Nanyin Zhang, Thesis Supervisor
  • William O Hancock, Honors Advisor
Keywords:
  • functional connectivity
  • nicotine
  • individual difference
  • acute response
Abstract:
Despite its potential as an addictive drug, the system level effect of nicotine on the brain remains elusive. The chronic effects of nicotine and the effect of abstinence on the brain were studied using fMRI at baseline, after seven days of exposure, and after more than twenty-four hours of abstinence. Elevated- plus maze (EPM) was completed after twenty-four hours of abstinence. Following exposure and abstinence, daily consumption was measured during a two-bottle choice (water or nicotine dissolved into water) period. Nicotine exposure significantly decreased time spent on the open arm of the EPM scores, whereas saline had no effect on time spent on the open arm of the EPM scores. Nicotine rats were divided between high and low consuming groups. The high consuming group included subjects with consumption of greater than fifty percent average nicotine-solution consumed (with respect to total volume consumed). Seed-based analysis with correlation to behavioral measures was completed for the chronic study. The fMRI data correlated with EPM identified unique patterns of functional connectivity (FC) correlated with EPM of the hippocampus and amygdala between the exposed and abstinent conditions. The data correlated with consumption also demonstrated unique patterns of FC correlated with consumption of the hippocampus and striatum between the exposed and abstinent conditions. These findings provided a whole brain picture of the functional connectivity changes correlated with either EPM or consumption. Seed-based analysis was also performed on high nicotine consuming groups (high NC) and low nicotine consuming (low NC) groups. Following a period of abstinence, the low NC group demonstrated FC between the accumbens and other striatal regions, while the high NC group did not demonstrate this FC with the accumbens. The diminished FC in the striatum following a period of abstinence in the high NC group may represent a lack of reward signaling. The low NC group also demonstrated intra-connectivity of the insula following more than twenty-four hours of abstinence, while the high NC group demonstrated no FC with the insula following the abstinence period. FC between the insula and the periaqueductal gray (PAG) was seen after nicotine exposure for the high NC group. These two FC patterns may serve as mechanisms of resilience (insula intra-connectivity) or vulnerability (insula−PAG connectivity) to nicotine addiction. Nicotine’s cognitive enhancing effects during acute exposure may underlie the rewarding effects that initiate addiction. Functional magnetic resonance imaging (fMRI) of Long Evans rats (n=30) was used to determine the relationship between acute nicotine exposure and FC changes. Drug naïve rats received a tail--vein catheter and received a 1-mL/kg dose of saline or nicotine (0.4 mg/kg-mL) and were imaged in an awake imaging paradigm. Seed-based analysis and independent component analysis were used to analyze the fMRI data. Functional connections between regions associated with chronic reward, sensory, and memory were implicated following a single acute nicotine exposure in drug-naïve rats.