Consistent with these findings, the dark/light box did not differentiate GDC-0152 between genotypes with respect to the primary outcomes of time and distance accumulation in the light field. However, an unbiased increase in total distance was revealed for B6eGFPChAT mice that is reflected by an increase in the total transitions between the dark and light fields.

Open field and dark/light box did not detect significantly anxiety-like differences between B6eGFPChAT and B6 control mice. However, B6eGFPChAT Inhibitors,research,lifescience,medical mice showed a moderate but significant bias to the open arms, suggesting that VAChT overexpression decreased anxiety-like behavior in the elevated plus maze. The decreased anxiety-like behavior observed in the elevated plus maze in the context of the released exploratory inhibition observed during each of the anxiety-like behavioral tasks suggests that the genetic modifications in the B6eGFPChAT have an anxiolytic effect. The divergent findings in the primary outcomes of the Inhibitors,research,lifescience,medical open field Inhibitors,research,lifescience,medical and dark/light box (no change in anxiety) and the elevated plus maze (decreased anxiety) can be reconciled as the former tasks may not provide the same

sensitivity as the elevated plus maze, which delivers a more complex anxiogenic insult (Crawley 2007). Alternatively, changes in the primary outcome of the elevated plus maze during VAChT overexpression may be solely based on the modified exploratory locomotion in the B6eGFPChAT Inhibitors,research,lifescience,medical mouse. Implications and concluding remarks In this study, we used congenic B6eGFPChAT mice that are homozygous for the RP23-268L19-EGFP transgene and have been previously characterized as Inhibitors,research,lifescience,medical having increased VAChT gene and protein expression (Nagy and Aubert 2012). These commercially available mice have been recently utilized during the investigation of multiple cholinergic pathways primarily for the identification and functional characterization of cholinergic neurons (Ade

et al. 2011; Krasteva et al. 2011; Ogura et al. 2011; Rosas-Ballina et al. 2011). Here, we identified that B6eGFPChAT mice present a unique behavioral phenotype compared with B6 controls. While it remains possible that the observed phenotype will be confounded by positional effects related Tolmetin to the random insertion of the BAC transgene, only a single commercially available B6eGFPChAT founder line exists precluding our examination using multiple founders with independent insertion sites. Keeping these limitations in mind, a cholinergic rationale related to the observed increase in VAChT protein and previously defined enhancement in ACh release (Nagy and Aubert 2012) is congruent with the data and it provides a plausible explanation to the observed behavior in B6eGFPChAT mice.