Potentiating action of MKC‐242, a selective 5‐HT_1A receptor agonist, on the photic entrainment of the circadian activity rhythm in hamsters

Abstract

1 Serotonergic projections from the midbrain raphe nuclei to the suprachiasmatic nuclei (SCN) are known to regulate the photic entrainment of circadian clocks. However, it is not known which 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the circadian regulation. In order to verify the role of 5-HT 1A receptors, we examined the e ects of 5-{3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]-propoxy}-1,3-benzodioxole HCl (MKC-242), a selective 5-HT 1A receptor agonist, on photic entrainment of wheel-running circadian rhythms of hamsters. 2 MKC-242 (3 mg kg 71 , i.p.) signi®cantly accelerated the re-entrainment of wheel-running rhythms to a new 8 h delayed or advanced light-dark cycle.

NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

“…As with the present findings, earlier reports noted that compounds acting at the 5HT1A receptor potentiate the response to light (Gannon, 2003;Gannon and Millan, 2006;Moriya et al, 1998;Rea et al 1995;Lall and Harrington, 2006). These studies, however, uniformly employed an experimental design in which animals were housed in constant darkness for several days prior to treatment.…”

“…the liver or lungs. MKC-242, a selective 5-HT1A partial agonist, is able to potentiate light-induced shifts in mice (Moriya et al, 1998;Takahashi et al, 2002); consequently, there is good reason to believe NAN-190 will also, offering the possibility of measuring similar effects on peripheral oscillators using luciferase reporter animals (e.g. Yoo et al, 2004).…”

Involvement of 5-HT3 and 5-HT4 Receptors in the Regulation of Circadian Clock Gene Expression in Mouse Small Intestine

“…Daily injection with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH DPAT) or MKC-242, selective 5-HT 1A receptor agonists, resulted in phase-advance of behavior rhythm when administered at subjective daytime (17,35). In this study, we did not examine whether daily injection of 5-HT 3 /5-HT 4 receptor agonists causes phaseshift in the circadian rhythm of clock gene expression in the small intestine.…”

“…When non-photic manipulations are presented during subjective day, the midbrain raphe nuclei and the thalamic intergeniculate leaflet convey non-photic information to the pacemaker in a 5-HT activity-dependent manner, leading to phase-shifting in the circadian rhythms (12,13). Further, 5-HT clockresetting is dependent on the activity of 5-HT 7 and/or 5-HT 1A receptors (14,15,16). In addition, non-photic phase shifts are brought about by 5-HT 7 (15 -17).…”

Two Distinct Serotonin Receptors Co-mediate Non-photic Signals to the Circadian Clock

“…This might mean that MKC-242 uses a different pathway(s) and/or mechanism from that of R(+)-8-OH-DPAT to induce phase shifts. In fact, the K i values of MKC-242 for 5-HT 1A and 5-HT 7 receptors are 0.35 nM and > 100 nM, respectively (12,13), which seems to cause differences in chronobiotic actions between MKC-242 and R(+)-8-OH-DPAT. Our previous study indicates that, unlike R(+)-8-OH-DPAT, MKC-242 potentiates photic entrainment by acting possibly on 5-HT 1A autoreceptors in the RN (13 (14).…”