Vesicular monoamine transporter 2 (VMAT2) as a potential mediator of social and repetitive behaviors in mice Open Access

Winokur, Emily Jordan (2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/bn999694w?locale=en
Published

Abstract

Vesicular monoamine transporter 2 (VMAT2) is a synaptic vesicle protein that packages monoamines (dopamine, serotonin, norepinephrine, and histamine) into synaptic vesicles. Aberrant VMAT2 functioning has been associated with disorders that often include symptoms such as depression, changes in fear responsiveness, social dysfunction, social anxiety, and an increased incidence of repetitive behaviors. It is likely that VMAT2 expression has an effect on social and repetitive behaviors as VMAT2 also has a role in the mesolimbic dopamine pathway, a pathway involved in social behavior, and VMAT2 is found in serotonergic neurons, also implicated in social and repetitive behaviors. Transgenic mice expressing 5% of the normal levels of VMAT2 and mice over-expressing VMAT2 provide a unique tool to study the contribution of VMAT2 to these behaviors. While previous research indicates changes in depressive- and anxiety-like behavior and changes in fear-like behavior in these transgenic mouse lines, little research has explored the effect of over- or under-expression of VMAT2 on social functioning and repetitive behaviors. This study uses a standard battery of mouse social tests to provide a basis for understanding how VMAT2 mediates social behavior and repetitive behaviors thus contributing to the development of pharmacological interventions as well as mouse models to study other disorders. Here, I show that the over- or under-expression of VMAT2 has no consistent effect on social behavior in mice. However, VMAT2 under-expression has an effect on the total time engaged in social behavior and the total time spent following a novel stimulus mouse. Additionally, I show that VMAT2 expression has an effect on repetitive behaviors such as self-grooming, digging, and jumping.

Table of Contents

Table of Contents

Abstract

1

Introduction

2

Methods

8

Results

12

Discussion

17

Figures

27

Supplemental Methods

35

Supplemental Figures

36

References

38

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