Cognitive performance in neurokinin 3 receptor knockout mice

Rationale The neurokinin 3 (NK(3)) receptor is a novel target under investigation for improvement of the symptoms of schizophrenia due to its ability to modulate dopaminergic signaling. However, research on effects of NK(3) antagonism with animal models has been hindered because of species differences in the receptor between humans, rats, and mice. Objectives The aim of the present study is to further knowledge on the role of NK(3) in cognitive functioning by testing the effect of knockout of the NK(3) receptor on tests of working memory, spatial memory, and operant responding. Materials and methods NK(3) knockout mice generated on a C57Bl/6 background were tested in delayed matching to position (DMTP), spontaneous alternation, Morris water maze, and active avoidance tasks. Results NK(3) knockout mice showed better performance in the DMTP task, though not delay dependently, which points to an effect on operant performance but not on working memory. No differences were seen between the groups in spontaneous alternation, another indication that working memory is not affected in NK(3) knockouts. There was no impairment in knockout mice in Morris water maze training, and the mice also showed faster response latency in the active avoidance task during training. Conclusions Collectively, these results support a role for the NK(3) receptor in performance of operant tasks and in spatial learning but not in working memory.