Development of Cell-Type-Specific Viral Vectors to Tease Apart the Neural Circuitry that Contributes to Drug Addiction - Viral Vector Approaches in Neurobiology and Brain Diseases - page 149

Chapter 8

Development of Cell-Type-Specifi c Viral Vectors to Tease
Apart the Neural Circuitry that Contributes to Drug
Addiction

Susan M. Ferguson and John F. Neumaier

Abstract

Although our understanding of the mechanisms that underlie drug addiction have advanced signifi cantly
over the past few decades, the lack of effi cacious treatments for this debilitating disorder suggest that there
is much work still to be done to clarify the role of specifi c cells and circuits in the process that govern addic-
tion. In recent years, new technologies have been developed that are now allowing researchers to express
transgenes in selective cell populations in the brain as well as to modulate the activity of these cell popula-
tions selectively. This chapter provides a detailed overview of how cell-type-specifi c viral vectors can be
developed and used in order to parse out the neural circuits that underlie addiction.

Key words Viral vector, Promoter, Drug addiction, Rodent, DREADD, Optogenetics, Cell specifi c,
Animal models

1 Introduction

Drug addiction has become a worldwide epidemic, with major
social and economic burdens on society. Despite the overwhelm-
ing negative consequences of addiction, the use and abuse of both
illicit drugs and prescription drugs continues to rise. The progres-
sion from initial drug exposure to regular drug use and ultimately
to compulsive habitual behavior and loss of inhibitory control
involves a series of molecular adaptations in discrete, functional
neurocircuits. A major goal of drug addiction research, therefore,
is to delineate the neural circuits that contribute to the underlying
pathophysiology that occurs both prior to the development of and
throughout the course of addiction. One informative way of
understanding this circuitry is to manipulate the neural circuits in
animal models such as locomotor sensitization to drugs of abuse or
drug self-administration paradigms. In addition, because the same
neural circuitry that contributes to drug addiction also underlies
normal reward and reinforcement processes, understanding the