Collectively, these data suggest that VAChT overexpression induces generalized locomotor hypoactivity that is unrelated to circadian sleep regulation. VAChT overexpression in B6eGFPChAT mice has not been targeted to specific brain regions, limiting the identification of specific brain areas responsible for the observed

hypoactivity. However, based on the discussion above, we postulate that VAChT overexpression is enhancing the inhibitory effect Inhibitors,research,lifescience,medical of ACh via cholinergic basal forebrain or dopaminergic striatal networks. Indeed, the decreased spontaneous activity exhibited by B6eGFPChAT mice is reminiscent of mouse models with increased ACh (via AChE inhibition) or decreased dopamine neurotransmission (Kobayashi et al. 1995; Zhou and Palmiter Inhibitors,research,lifescience,medical 1995). Confirmation of these potential mechanisms awaits region-specific VAChT overexpression models. Exploratory behavior Novel stimuli, including new or modified environments, generate selleckchem approach/avoidance conflicts in mice.

The conflict tests the balance between exploring the novelty to gain information and the anxiety-related cautiousness to avoid danger or harm. Exposure to novel stimuli has been extensively associated with cholinergic activation. Studies using exposure to novel environments and sensory stimulation as the experimental paradigms have also shown Inhibitors,research,lifescience,medical increased ACh release in the nucleus accumbens, hippocampal formation, and cortical Inhibitors,research,lifescience,medical structures (Thiel et al. 1998; Schildein et al. 2000; Giovannini et al.

2001). Furthermore, a thing number of studies have demonstrated that cortical (Day et al. 1991), striatal (Cohen et al. 2012), and hippocampal (Dudar et al. 1979; Day et al. 1991; Mizuno et al. 1991). ACh release is positively correlated to behavioral arousal in novel environments as defined by locomotor activity. We therefore investigated the exploratory behavior in B6eGFPChAT mice in novel environments to evaluate the Inhibitors,research,lifescience,medical contribution of VAChT overexpression. The results from the open field experiments indicate that B6eGFPChAT mice display transient Anacetrapib increases in activity upon initial exposure to the novel environment compared to B6 control mice, including increased horizontal activity and rearing. These increased levels of exploration return to normal following the first 10 min of the open field exposure, where B6eGFPChAT mice begin to elicit normal intrasession patterns of habituation. Upon repeated exposure to the novel environment, B6eGFPChAT mice displayed only a modest decrease in locomotion, which did not reach significance, and was found to be significantly different than B6 control mice by day 3. The intrasession and intersession habituation patterns of B6 control mice were found to be consistent with previous reports (Bolivar et al. 2000; Bolivar and Flaherty 2003).