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SLEEP AND BIOLOGICAL RHYTHMS

Acute ethanol impairs photic and nonphotic circadian phase resetting in the Syrian hamster

¹Department of Biological Sciences, Kent State University, Kent, Ohio; and ²Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee

Submitted 17 September 2008 ; accepted in final form 3 December 2008

Disrupted circadian rhythmicity is associated with ethanol (EtOH) abuse, yet little is known about how EtOH affects the mammalian circadian clock of the suprachiasmatic nucleus (SCN). Clock timing is regulated by photic and nonphotic inputs to the SCN involving glutamate release from the retinohypothalamic tract and serotonin (5-HT) from the midbrain raphe, respectively. Our recent in vitro studies in the SCN slice revealed that EtOH blocks photic phase-resetting action of glutamate and enhances the nonphotic phase-resetting action of the 5-HT_1A,7 agonist, 8-OH-DPAT. To explore the basis of these effects in the whole animal, we used microdialysis to characterize the pharmacokinetics of intraperitoneal injection of EtOH in the hamster SCN extracellular fluid compartment and then studied the effects of such EtOH treatment on photic and serotonergic phase resetting of the circadian locomotor activity rhythm. Peak EtOH levels (50 mM) from a 2 g/kg injection occurred within 20–40 min with a half-life of 3 h. EtOH treatment dose-dependently attenuated photic phase advances but had no effect on phase delays and, contrary to in vitro findings, markedly attenuated 8-OH-DPAT-induced phase advances. In a complementary experiment using reverse microdialysis to deliver a timed SCN perfusion of EtOH during a phase-advancing light pulse, the phase advances were blocked, similar to systemic EtOH treatment. These results are evidence that acute EtOH significantly affects photic and nonphotic phase-resetting responses critical to circadian clock regulation. Notably, EtOH inhibition of photic signaling is manifest through direct action in the SCN. Such actions could underlie the disruption of circadian rhythmicity associated with alcohol abuse.

suprachiasmatic nucleus; glutamate; serotonin; microdialysis; alcohol

This article has been cited by other articles:

				C. L. Ruby, A. J. Brager, M. A. DePaul, R. A. Prosser, and J. D. Glass Chronic ethanol attenuates circadian photic phase resetting and alters nocturnal activity patterns in the hamster Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R729 - R737. [Abstract] [Full Text] [PDF]

				J. A. Seggio, M. C. Fixaris, J. D. Reed, R. W. Logan, and A. M. Rosenwasser Chronic Ethanol Intake Alters Circadian Phase Shifting and Free-Running Period in Mice J Biol Rhythms, August 1, 2009; 24(4): 304 - 312. [Abstract] [PDF]