Using Viral-Mediated Gene Transfer to Study Depressive- Like Behavior - Viral Vector Approaches in Neurobiology and Brain Diseases - page 170

a greater preference for saccharin. However, we found no effect of
increased 5-HT 1B expression on social defeat stress-induced reduc-
tion in hedonic responses (Nair, submitted for publication). Thus,
in the context of our larger body of work, we concluded that these
5-HT 1B receptors can alter artifi cial drug rewards but not natural
rewards such as a sweetened solution.

Vignette #2
Previous work from our group and others has clearly demonstrated
that distinct subregions of DRN have different afferent and efferent
connections [ 19 ] and differential effects on different emotional
behaviors such as fear, anxiety, and depression-like behavior. Since
our previous work showed that the ventromedial DRN was impor-
tant in anxiety-like behavior, and since the caudal DRN is stress
sensitive, we wanted to determine the role of 5-HT 1B autoreceptors
that expressed in this region and transported to axon terminals, and
their role in mediating fear and anxiety. Once again, we took advan-
tage of the transient expression levels of HSV vectors to express
5-HT 1B receptors in the DRN either during training and acquisition
of conditioned fear or during expression of the learned behavior. We
timed gene transfer (either 5-HT 1B /GFP or GFP alone to occur
either 3 days prior to fear conditioning or 3 days prior to fear testing
in two separate experiments). In the fi rst experiment, we allowed
enough time to elapse after fear conditioning so that transgenic
5-HT 1B overexpression had dissipated. We were able to show that
receptor overexpression during acquisition of behavior did not alter
the acquisition of conditioned fear behavior, whereas when increased
5-HT 1B autoreceptor expression occurred during expression of pre-
viously conditioned fear, the behavior was disrupted, suggesting
that 5-HT 1B autoreceptors in the caudal DRN neurons projections
regulate only the behavioral expression of conditioned fear.

5 Conclusion

In conclusion, working with viral vectors poses certain challenges
that range from governmental and institutional oversight and regu-
lations to experimental design considerations. Once biosafety prac-
tices are in place, careful designing of experiments can yield very
useful information about complex animal behaviors that may even-
tually shed light onto complex human behaviors or enable us to
treat certain dysfunctional aspects of behavior. Some of the issues
that are most important to the success of a viral expression behavior
experiment include paying attention to the timing, localization,
and duration of gene expression in relation to key elements of the
behavioral testing procedure. Further, optimizing stereotaxic pro-
cedures so that maximal transgene expression occurs at the key
time points in the experiment, and histological confi rmation of