Effect of Neuropeptide Y Y2 Receptor Deletion on Emotional Stress-Induced Neuronal Activation in Mice

KEY WORDS anxiety; c-Fos mapping; elevated plus maze; neuropeptide Y; Y2 receptor knockout mice ABSTRACT In different behavioral paradigms including the elevated plus maze (EPM), it was observed previously that deletion of the neuropeptide Y Y2 receptor sub-type results in potent suppression of anxiety-related and stress-related behaviors. To identify neurobiological correlates underlying this behavioral reactivtiy, expression of c-Fos, an established early marker of neuronal activation, was examined in Y2 recep-tor knockout (Y22/2) vs. wildtype (WT) mice. Mice were placed on the open arm (OA) or closed arm (CA) of the EPM for 10 min and the effect on regional c-Fos expression in the brain was investigated. The number of c-Fos positive neurons was significantly increased in both WT and Y22/2 lines after OA and CA exposure in 51 of 54 regions quantified. These regions included various cortical, limbic, thalamic, hypothalamic, and hindbrain regions. Genotype influenced c-Fos responses to arm exposures in 6 of the 51 activated regions: the cingulate cortex, barrel field of the primary somatosen-sory cortex, nucleus accumbens, dorsal lateral septum, amygdala and lateral periaque-ductal gray. These differences in neuronal activity responses to the novel environ-ments were more pronounced after OA than after CA exposure. Mice lacking Y2 recep-tors exhibited reduced neuronal activation when compared to WT animals in response to the emotional stressors. Reduced neuronal excitability in the identified brain areas relevant to the processing of motivated, explorative as well as anxiety-related behav-iors is suggested to contribute to the reduced anxiety-related behavior observed in Y22/2 mice. Synapse 63:236–246, 2009. VC 2008 Wiley-Liss, Inc