Serotonin1A autoreceptor activation by S 15535 enhances circadian activity rhythms in hamsters: Evaluation of potential interactions with serotonin2A and serotonin2C receptors

摘要: Abstract Mammalian circadian activity rhythms are generated by pacemaker cells in the suprachiasmatic nucleus (SCN). As revealed actions of diverse agonists, serotonergic input from raphe nuclei generally inhibits photic signaling nucleus. In contrast, serotonin (5HT) 1A partial agonist, 4-(benzodioxan-5-yl)1-(indan2-yl)piperazine (S 15535), was found to enhance phase-shifting influence light on hamster [Gannon, Neuroscience 119 (2003) 567]. Herein, we extend this observation showing that S 15535 (5.0mg/kg, i.p.) markedly (275%) enhanced light-induced phase shift rhythms: further, action dose-dependently abolished highly-selective 5HT receptor antagonist, WAY 100,635 ( N -[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl] -2-pyridinyl-cyclohexane-carboxamide maleate) (0.1–0.5mg/kg, i.p.). 100,635, which inactive alone, shares antagonist at postsynaptic sites, yet blocks its effects their presynaptic counterparts. Thus, autoreceptor activation must be involved effect contrasts with opposite, inhibitory upon shifts “full” 8-OH-DPAT, acts stimulation receptors [ Rea et al., J Neurosci 14 (1994) 3635]. Despite occurrence 2A and 2C rat ) nucleus, is unknown since selective ligands have never been evaluated. This issue investigated most agents currently available. However, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.25 0.5mg/kg), α -6-chloro-5-fluoro-a-methyl-1 H -indole-1-ethanamine fumarate (Ro-60-0175) (1.0 5.0mg/kg), failed affect hamsters. Moreover, even over broad dose-ranges, (+)-(2,3-dimethoxy-phenyl)-{1-[2-(4-fluoro-phenyl)-ethyl]-piperidin-4-yl}methanol (MDL 100,907) (0.1–1.0mg/kg), 6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy)pyridin-3-yl carbamoyl]indoline (SB 242,084) (1.0–10.0mg/kg), were likewise inactive. view evidence sites functionally interact receptors, also examined these 15535, but no significant alteration seen enhancement rhythms. conclusion, elicits a striking specifically recruiting autoreceptors, leads suppression Surprisingly, for role or found, though comparable functional studies remain undertaken rats. Indeed, present work underlines importance comparative various species, as well need further study potential interactions among subtypes control.