Year: 2010
Type: article
Abstract: 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-HT1A,7 agonist, 8-OH-DPAT.To explore the basis of these effects in the whole animal we used microdialysis to characterize the pharmacokinetics of i.p. 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-DPATinduced phase-advances.In a complementary experiment using reverse-microdialysis to
Author: Christina L. Ruby
Institution: Kent State University
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W2499182565