Defense Date

2012

Document Type

Thesis

Degree Name

Master of Science

Department

Pharmacology & Toxicology

First Advisor

Darlene Brunzell

Second Advisor

Xiangning Chen

Third Advisor

Keith Shelton

Abstract

Tobacco dependence is high in women who suffer from anxiety disorders yet little is known about the contributions of nicotinic acetylcholine receptors (nAChRs) on anxiety-like behavior. β2*nAChRs (*denotes assembly with other subunits) are the most abundantly expressed nAChRs in the brain yet little is known about the contributions of β2*nAChRs on anxiety-like behavior in female mice. In this study, antagonism and nicotine effects on anxiety-like behavior was investigated across the life span in 6, 12 and 24-month-old drug-naïve knockout (KO), heterozygous (HET) and a gain of function α6L9S mice and wild type (WT). HET mice showed increased sensitivity to di-hydrobeta-erythroidine compared to WT mice. Aged mice showed decreased locomotor activity and exploratory behavior compared to younger mice. Low doses of nicotine produced anxiolytic-like effects, whilst a high dose of nicotine produced anxiogenic-like effects. Activation of the α6*nAChRs supports an anxiolysis-like phenotype. These results implicate α4β2*nAChRs and α6β2*nAChRs in anxiety-like behavior.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-11-2012

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