Adenosine A 1 receptors regulate the response of the hamster circadian clock to light

Abstract

Circadian rhythms are synchronized to the environmental light–dark cycle by daily, light-induced adjustments in the phase of a biological clock located in the suprachiasmatic nucleus. Ambient light alters the phase of the clock via a direct, glutamatergic projection from retinal ganglion cells. We investigated the hypothesis that adenosine A 1 receptors modulate the phase adjusting effect of light on the circadian clock. Systemic administration of the selective adenosine A 1 receptor agonist, N 6-cyclohexyladenosine (CHA), significantly ( p<0.05) attenuated light-induced phase delays and advances of the circadian activity rhythm. Selective agonists for the adenosine A 2A and adenosine A 3 receptors were without effect. The inhibitory effect of CHA on light-induced phase advances was dose-dependent (0.025–1.0 mg/kg, ED 50=0.3 mg/kg), and this effect was blocked in a dose-dependent (0.005–1.0 mg/kg) manner by the adenosine A 1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Injection of CHA (10 μM) into the region of the suprachiasmatic nucleus significantly attenuated light-induced phase advances, and this effect was also blocked by DPCPX (100 μM). The results suggest that adenosine A 1 receptors located in the region of the suprachiasmatic nucleus regulate the response of the circadian clock to the phase-adjusting effects of light.