Sleep disturbance induced by substance P in mice

Substance P (SP) and neurokinins have been implicated in modulating pain and mood but little is known about their effect on sleep–wake behavior. The purpose of the present study was to examine the possible involvement of SP in sleep–wake mechanisms without activation of painful responses. Electrophysiological recordings of the sleep–wake cycle were conducted in C57BL/6J male mice that had intracerebral ventricular cannula inserted for drug administration. Initially, in order to determine the highest dose of SP that would not induce nociceptive response, 10 animals per group received administration of either SP doses or artificial cerebrospinal fluid (CSF-sham group) through the cannula and were assessed by the hot plate test. The sleep–wake cycle of two other groups of mice was recorded for 24 h before (baseline) and after receiving CSF (n = 10) or SP-1 mM (n = 11), dose that had been determined in the previous hot plate test. SP interfered with sleep, when compared to baseline and to sham group, by reducing sleep efficiency, increasing latency of sleep and the number of awakening bouts. To examine the reversal of SP effects, eight mice were administered with an NK1 receptor antagonist before SP administration. Prior administration of the NK1 antagonist prevented the disturbances in sleep. Conclusions: The results suggest that SP produces disturbances in sleep, likely mediated by the NK1 receptor.