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 effects 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⁻¹, i.p.) significantly accelerated the re-entrainment of wheel-running rhythms to a new 8 h delayed or advanced light-dark cycle.

3. MKC-242 (3 mg kg⁻¹, i.p.) also potentiated the phase advance of the wheel-running rhythm produced by low (5 lux) or high (60 lux) intensity light pulses. In contrast, 8-hydroxy-dipropylaminotetralin (8-OH-DPAT)(5 mg kg⁻¹, i.p.), a well known 5-HT_1A/5-HT₇ receptor agonist, only suppressed low intensity (5 lux) light-induced phase advances.

4. The potentiating actions of MKC-242 on light pulse-induced phase advances were observed even when injected 20 or 60 min after the light exposure.

5. The potentiating action of MKC-242 was antagonized by WAY100635, a selective 5-HT_1A receptor blocker, but not by ritanserin, a 5-HT₂/5-HT₇ receptor blocker, indicating that MKC-242 is activating 5-HT_1A receptors.

6. Light pulse-induced c-fos expression in the SCN and the intergeniculate leaflet (IGL) were unaffected by MKC-242 (3 mg kg⁻¹, i.p.).

7. HPLC analysis demonstrated that MKC-242 (3 mg kg⁻¹, i.p.) decreased the 5-HIAA content in the SCN.

8. The present results suggest that presynaptic 5-HT_1A receptor activation may be involved in the potentiation of photic entrainment by MKC-242 in hamsters.

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