There is abundant evidence linking brain monoamine neurotransmitter systems to behaviors such as alcoholism, aggression, reward, and psychiatric states including depression and schizophrenia. The evidence consists of correlations between monoamine levels and psychiatric disease and behavior in humans and drug effects in humans and experimental animals. The next step is to link specific molecules with behavioral effects. Our approach to this issue is to use viral vectors to deliver constructs that will modulate the level of specific behaviorally relevant proteins in vivo. We have produced a defective herpes virus which overexpresses the rat serotonin transporter (5-HTT). The 5-HTT is the target for the serotonin specific reuptake inhibitors e.g. fluoxetine (Prozac TM) and a candidate gene in psychiatric diseases. The 5-HTT virus has been shown to be functional when injected into the rat brain. The biochemical and behavioral effects of overexpressing the 5-HTT in the raphe nuclei are now being examined.
| Ni, Yajin; Goldman, D; Hoffman, B et al. (2003) Overexpression of an epitope-tagged serotonin transporter in serotonin neurons of the dorsal raphe nucleus using a defective HSV-1 vector. Behav Brain Res 138:133-43 |
