An NK1 receptor antagonist affects the circadian regulation of locomotor activity in golden hamsters

Substance P (SP) is a neuromodulator which may participate in the photic regulation of the circadian timing system in mammals. The biological effects of SP are mediated by interaction with specific receptors, designated as NK₁, NK₂, and NK₃. The NK₁ subtype receptor is expressed in the circadian system. Experiment 1 was designed to test whether an NK₁ antagonist mimics the effects of dark pulses. Hamsters were housed in constant lighting conditions, either constant darkness or constant light (around 250 lx), and they received an i.p. injection of either the specific NK₁ receptor antagonist, L-760,735 (5 mg/kg), or saline during the mid-subjective day, a time when dark pulses cause a phase-advance in circadian rhythm of locomotor activity. After treatment with the NK₁ antagonist, significant phase-advances of wheel-running activity rhythm were found in constant light, but not in constant darkness. Experiment 2 was designed to test the ability of the NK₁ antagonist to block the phase-delaying and/or the phase-advancing effects of light in animals kept in constant darkness. Phase-advances of locomotor activity rhythm that can normally be induced by light pulses given during the late subjective night were markedly reduced by pre-treatment with the NK₁ antagonist. By contrast, phase-delays that can be induced by lights pulses given during the early subjective night were unaffected by the NK₁ antagonist. These data support the hypothesis that SP within the circadian system may, by interacting with NK₁ receptors, modulate photic responses of the SCN pacemaker.