Protein-synthesis inhibitor blocks (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)- or substance P-induced phase shift of the circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro

The mammalian suprachiasmatic nucleus (SCN) has been identified as a circadian pacemaker. N-methyl-d-aspartate (NMDA), non-NMDA and substance P receptors have been suggested to be involved in handling of photic information in the SCN. In the Aplysia eyes, in which the circadian clocks are involved, serotonin- or cAMP-induced phase changes of the circadian rhythm were reported to be blocked by protein-synthesis inhibitors. Therefore, we investigated whether protein-synthesis inhibitor can block the non- NMDA receptor agonist (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA)- or substance P (SP)-induced phase changes of SCN activity rhythm. Although application of 10 μM cycloheximide alone during the early part of the subjective night did not cause phase change, it blocked both 10 μM AMPA- and 1 μM SP-induced phase delay. The present result suggests that protein synthesis may be required in the manifestation of AMPA- and SP-induced phase change of circadian clock.