title: Impaired arousal in rat pups with prenatal alcohol exposure is modulated by GABAergic mechanisms.
abstract: Prenatal alcohol exposure (PAE) increases the risk for The Sudden Infant Death Syndrome (SIDS) in human infants. In rat pups, the arousal response to hypoxia is modulated by medullary raphe GABAergic mechanisms. We hypothesized that arousal to hypoxia is impaired by PAE, and is associated with an increase in medullary GABA and enhanced GABAergic activity. Pregnant dams received an ethanol liquid diet (ETOH), an iso-caloric pair fed diet (PF) or a standard chow diet (CHOW). We first measured the time to arousal (latency), during four episodes of hypoxia in P5, P15, and P21 CHOW, PF, and ETOH pups. We also measured brainstem GABA concentration in the same groups of pups. Finally, we injected artificial cerebrospinal fluid (aCSF), nipecotic acid (NIP) or gabazine into the medullary raphe of P15 and P21 pups receiving the three diets. For statistical analysis, the PF and CHOW groups were combined into a single CONTROL group. Our main finding was that compared to CONTROL, arousal latency to hypoxia is increased in ETOH pups at P15 and P21, and the concentration of brainstem GABA is elevated at P21. NIP administration in CONTROL pups led to arousal latencies similar in magnitude to those in ETOH pups after aCSF injection. NIP injected ETOH pups had no further increases in arousal latency. We conclude that PAE impairs arousal latency and this is mediated or modulated by medullary GABAergic mechanisms.
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire chrystelle.sirieix@gmail.com.
authors.forename: Chrystelle M
authors.initials: CM
authors.lastname: Sirieix
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Tobia
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schneider
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire Department of Pediatrics, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Darnall
keywords: Arousal; GABA; hypoxia; prenatal alcohol exposure