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 154

Fig. 2 Neuropeptide promoters target gene expression to specifi c cell phenotypes. Hemagglutinin (HA)-tagged
G s -coupled DREADD (D-s) receptors are selectively expressed in substance P (SP)-containing medium spiny
striatal neurons following infusions of an HSV viral vector that uses the dynorphin promotor to drive gene
expression. Green , HA; red , SP; yellow colocalization of neurons. Scale bars represent 25 μ m

the hemagglutinin-tagged transgenic receptor protein and key cell
markers. For example, we fi nd that when we used the preprodyn-
orphin promoter to drive transgene expression, almost all of the
hemagglutinin immunoreactivity is contained within cell bodies
that also express substance P, a marker for striatonigral neurons
(Fig. 2 ) [ 9 ]. Once in vivo cell-specifi city is confi rmed, experiments
using animal models of addiction can be performed. There are a
variety of animal models of drug addiction, including drug self-
administration, locomotor sensitization, and conditioned place
preference, all of which can be used with viral vector techniques.
Although it is beyond the scope of this chapter to describe each
animal model along with its advantages and limitations, detailed
protocols for addiction-related animal models can be readily found
in the existing literature (see, for example [ 18 ]). Once the animal
species have been chosen, there are a number of other factors to
consider prior to starting the experiment. For example, it is also
necessary to decide whether the experiments will be conducted
using a reverse light-dark cycle, in an enriched environment, and if
food restriction will be used. All of these variables can infl uence the
duration of training as well as the experimental outcome and
should be carefully considered. All methods and procedures that
are used on animals must be conducted in accordance with the
proper regulatory agencies.

3 Methods

1. Once the animals arrive into the animal facility, they should be
given an acclimation period of at least 5 days prior to experi-
mental manipulation. However, after a 2-day acclimation, the