Using Viral-Mediated Gene Transfer to Study Depressive- Like Behavior - Viral Vector Approaches in Neurobiology and Brain Diseases - page 168

Fig. 1 Time course of HSV expression and opportunities for behavior analysis. ( 1 ) Behavior can be recorded
before any manipulation takes place; this is the purest expression of baseline behavior; ( 2 ) surgery itself can
affect animal behavior and recovery time must be allowed so assays must be planned accordingly; ( 3 ) baseline
behavior can be recorded after surgery and will refl ect the effects of the surgical procedure; ( 4 ) it is essential
to determine the peak expression time of a viral vector, since expression time and intensity can be affected by
promoter choice and other factors; ( 5 ) behavior can be assayed shortly after viral expression dissipates; this
captures behavioral changes over short time scales; ( 6 ) long-term effects of viral expression can be assayed
weeks or even months after viral expression dissipates
Vignettes
In order to illustrate the chain of events that leads us from experi-
mental plan to data collection, we will present two vignettes. See
Fig. 1 for a graphic representation of viral expression and design
considerations.
Vignette #1
5-HT 1B receptors in the mesolimbic reward pathway, specifi cally
those expressed on GABAergic projection neurons emanating
from the striatum and terminating in the basal ganglia [ 15 ] have
been shown to be regulated by cocaine, alcohol, and chronic social
stress [ 16 - 18 ]. We postulated that this upregulation was due to
compensatory adaptation (i.e., if these receptors in this pathway
modulate the rewarding effects of drugs of abuse and they upregu-
late during chronic social stress, this might constitute a
compensatory adaptation that diminishes the impact of aversive
stimuli and enhances pleasurable experiences). Therefore, we
planned to manipulate 5-HT 1B receptors at discrete time intervals
during social stress exposure to determine if receptor expression
altered behavioral outcomes after stress. In other words, to answer
the question: could hedonic defi cits that occur after stress be res-
cued? HSV is an ideal vector for this because it is transiently
expressed, allowing us to upregulate 5-HT 1B receptor expression
during specifi c intervals during stress exposure or behavioral test-
ing. We hypothesized that enhancing 5-HT 1B receptor levels dur-
ing chronic social stress would improve depressive-like behavioral