Adenosine A1 receptors regulate the response of the hamster circadian clock to light

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, ED50 = 0.3 mg/kg), and this effect was blocked in a dose-dependent (0.005-1.0 mg/kg) manner by the adenosine A, receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Injection of CHA (10 <mu>M) into the region of the suprachiasmatic nucleus significantly attenuated light-induced phase advances, and this effect was also blocked by DPCPX (100 muM). The results suggest that adenosine A, receptors located in the region of the suprachiasmatic nucleus regulate the response of the circadian clock to the phase-adjusting effects of light. (C) 2001 Published by Elsevier Science B.V.