The observation that the maximum effect of the virus infusion on the behavior occurs on 18th day of viral infusion correlates with our work where we showed that the Ad-shα4-1 virus down-regulates mRNA and protein levels of the α4 subunit transiently, with significant reductions 18 days after infusion and recovery 25 days after infusion (Rewal et al. 2009). In addition, we previously demonstrated that decreases in α4 expression after in vivo infusion of the Ad-sh4-1 virus into the NAc shell were not accompanied by compensatory changes in the expression of the mRNA or protein for the δ, α1, β2 and γ2 subunits (Rewal et al. 2009). Although we cannot rule out cellular changes that may serve to compensate for changes in the general level of inhibition of affected neurons, it is likely that our manipulation produced minimal changes in other GABAergic receptors given the lack of evidence for changes in many of the subunits.
