Effects of neurotensin on discharge rates of rat suprachiasmatic nucleus neurons in vitro

The neuropeptide neurotensin and two classes of its receptors, the neurotensin receptor-1 and 2, are present in the suprachiasmatic nucleus of the mammalian hypothalamus. The suprachiasmatic nucleus houses the mammalian central circadian pacemaker, but the effects of neurotensin on cellular activity in this circadian pacemaker are unknown. In this study, we examined the effects of neurotensin on the spontaneous discharge rate of rat SCN cells in an in vitro slice preparation. Neurotensin (1-10 μM) increased cell firing rate in ∼50% of cells tested, while ∼10% of suprachiasmatic cells tested showed a decrease in firing rate in response to neurotensin. These effects of neurotensin were not altered by the GABA receptor antagonist bicuculline (20 μM) or the glutamate receptor antagonists, D-aminophosphopentanoic acid (50 μM) and 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM). The neurotensin receptor selective antagonists SR48692 and SR142948a (10 μM) failed to antagonise neurotensin responses in the majority of cells examined. Compounds that function as agonists selective for the neurotensin-receptor subtypes 1 and 2, JMV-510 and JMV-431 respectively, elicited neurotensin-like responses in ∼90% of cells tested. Six out of seven cells tested responded to both JMV-510 and JMV-431. Neuropeptide Y (100 nM) treatment of suprachiasmatic nucleus slices was found to elicit profound suppression of neuronal firing rate. Co-application of neurotensin with neuropeptide Y significantly (P