PHASE ADVANCES OF CIRCADIAN-RHYTHMS IN SOMATOSTATIN DEPLETED RATS - EFFECTS OF CYSTEAMINE ON RHYTHMS OF LOCOMOTOR-ACTIVITY AND ELECTRICAL-DISCHARGE OF THE SUPRACHIASMATIC NUCLEUS

Somatostatin is synthesized in the suprachiasmatic nucleus (SCN), a ci rcadian pacemaker in mammals. To explore the functional significance o f somatostatin in the circadian system, we examined rhythms of rat loc omotor activity and electrical firing rate of SCN neurons in the brain slice after temporal depletion of somatostatin levels in the SCN. Int raperitoneal administration of cysteamine (200 mg/kg), a somatostatin depletor, significantly reduced somatostatin level in the in vivo SCN 5 min after injection and kept low level as long as 3 to 4 days. This administration, on the other hand, induced significant phase advances of about 51 min in the subsequent free-running rhythm of locomotor act ivity of the rat. A marked phase advance in the circadian rhythm of fi ring rate in the SCN was also observed after administration of cysteam ine in coronal hypothalamic slices. These persistent phase shifts afte r administration of a somatostatin depletor may suggest that the chang e of somatostatin level in the SCN have a feedback influence on the ci rcadian pacemaker.