Behavioral characterization of the hyperphagia synphilin-1 overexpressing mice.

Synphilin-1 is a cytoplasmic protein that has been shown to be involved in the control of energy balance. Previously, we reported on the generation of a human synphilin-1 transgenic mouse model (SP1), in which overexpression of human synphilin-1 resulted in hyperphagia and obesity. Here, behavioral measures in SP1 mice were compared with those of their age-matched controls (NTg) at two time points: when there was not yet a group body weight difference ("pre-obese") and when SP1 mice were heavier ("obese"). At both time points, meal pattern analyses revealed that SP1 mice displayed higher daily chow intake than non-transgenic control mice. Furthermore, there was an increase in meal size in SP1 mice compared with NTg control mice at the obese stage. In contrast, there was no meal number change between SP1 and NTg control mice. In a brief-access taste procedure, both "pre-obese" and "obese" SP1 mice displayed concentration-dependent licking across a sucrose concentration range similar to their NTg controls. However, at the pre-obese stage, SP1 mice initiated significantly more trials to sucrose across the testing sessions and licked more vigorously at the highest concentration presented, than the NTg counterparts. These group differences in responsiveness to sucrose were no longer apparent in obese SP1 mice. These results suggest that at the pre-obese stage, the increased trials to sucrose in the SP1 mice reflects increased appetitive behavior to sucrose that may be indicative of the behavioral changes that may contribute to hyperphagia and development of obesity in SP1 mice. These studies provide new insight into synphilin-1 contributions to energy homeostasis.