Consequences of gestational stress on GABAergic modulation of respiratory activity in developing newborn pups.

TitleConsequences of gestational stress on GABAergic modulation of respiratory activity in developing newborn pups.
Publication TypeJournal Article
Year of Publication2014
AuthorsDelhaes, F, Fournier, S, Tolsa, J-F, Peyter, A-C, Bairam, A, Kinkead, R
JournalRespir Physiol Neurobiol
Volume200
Pagination72-9
Date Published2014 Aug 15
ISSN1878-1519
KeywordsAnimals, Animals, Newborn, Brain Stem, Cervical Vertebrae, Dose-Response Relationship, Drug, Female, GABA-A Receptor Agonists, gamma-Aminobutyric Acid, Male, Muscimol, Plethysmography, Whole Body, Pregnancy, Prenatal Exposure Delayed Effects, Random Allocation, Rats, Sprague-Dawley, Receptors, GABA-A, Respiration, Sex Characteristics, Spinal Cord, Stress, Psychological, Tissue Culture Techniques
Abstract

The GABAergic system modulates respiratory activity and undergoes substantial changes during early life. Because this maturation process is sensitive to stress, we tested the hypothesis that gestational stress (GS) alters development of GABAergic modulation of respiratory control in rat pups. The respiratory responses to the selective GABAA receptor agonist muscimol were compared between pups born to dams subjected to GS (bright light and predator odor; 20 min/day from G9 to G19) or maintained under standard (control) conditions. Respiratory activity was measured on 1 and 4 days old pups of both sexes using in vivo (whole body plethysmography) and in vitro (isolated brainstem-spinal cord preparation) approaches. In intact pups, muscimol injection (0.75 mg/kg; i.p.) depressed minute ventilation; this response was less in GS pups, and at P4, muscimol augmented minute ventilation in GS females. Bath application of muscimol (0.01-0.5 μM) onto brainstem preparations decreased inspiratory (C4) burst frequency and amplitude in a dose-dependent manner; the responsiveness decreased with age. However, GS had limited effects on these results. We conclude that the results obtained in vivo are consistent with our hypothesis and show that GS delays maturation of GABAergic modulation of respiratory activity. The differences in the results observed between experimental approaches (in vivo versus in vitro) indicate that the effect of prenatal stress on maturation of GABAergic modulation of respiratory control mainly affects the peripheral/metabolic components of the respiratory control system.

DOI10.1016/j.resp.2014.05.015
Alternate JournalRespir Physiol Neurobiol
PubMed ID24929063
Grant ListMOP119337 / / Canadian Institutes of Health Research / Canada