Adenosine is widely accepted to act as an inhibitory neuromodulator in the mammalian central nervous system. In the present study, we examined whether adenosine receptor agonist modifies the photic entraining responses in the rat suprachiasmatic nucleus both in vivo and in vitro. Light (200 lux, 15 min)-induced phase shifts of hamster wheel-running rhythms was attenuated by a systemic administration of A1-adenosine receptor agonist N6-cyclohexyladenosine (N-CHA) in a dose-dependent manner; 0.5 mg/kg N-CHA caused 60% inhibition of light-induced phase shifts. On the other hand, A2-adenosine receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) failed to inhibit light-induced phase shifts. Systemic administration of N-CHA but not of DPMA inhibited light (300 lux, 1 h)-induced Fos expression in the suprachiasmatic nucleus in a dose-dependent manner; 1 mg/kg N-CHA caused 73% inhibition of light-induced Fos expression. Bath application of N-CHA but not of DPMA inhibited optic nerve stimulation-evoked field potentials in rat suprachiasmatic nucleus slices. The present results suggest that activation of adenosine A1-receptor attenuates the photic input through the inhibition of retinohypothalamic pathway to the SCN.
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