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Neonatal maternal separation and enhancement of the hypoxic ventilatory response in rat: the role of GABAergic modulation within the paraventricular nucleus of the hypothalamus
Author(s) -
Genest SophieEmmanuelle,
Balon Norbert,
Laforest Sylvie,
Drolet Guy,
Kinkead Richard
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.135160
Subject(s) - microinjection , bicuculline , hypoxic ventilatory response , gabaergic , hypothalamus , gabaa receptor , muscimol , endocrinology , medicine , control of respiration , chemistry , excitatory postsynaptic potential , gaba receptor antagonist , receptor , nucleus , respiratory system , biology , neuroscience
Neonatal maternal separation (NMS) affects respiratory control development as adult male (but not female) rats previously subjected to NMS show a hypoxic ventilatory response 25% greater than controls. The paraventricular nucleus of the hypothalamus (PVN) is an important modulator of respiratory activity. In the present study, we hypothesized that in awake rats, altered GABAergic inhibition within the PVN contributes to the enhancement of hypoxic ventilatory response observed in rats previously subjected to NMS. During normoxia, the increase in minute ventilation following microinjection of bicuculline (1 m m ) within the PVN is greater in NMS versus control rats. These data show that regulation of ventilatory activity related to tonic inhibition of the PVN is more important in NMS than control rats. Microinjection of GABA or muscimol (1 m m ) attenuated the ventilatory response to hypoxia (12% O 2 ) in NMS rats only. The higher efficiency of microinjections in NMS rats is supported by results from GABA A receptor autoradiography which revealed a 22% increase in GABA A receptor binding sites within the PVN of NMS rats versus controls. Despite this increase, however, NMS rats still show a larger hypoxic ventilatory response than controls, suggesting that within the PVN the larger number of GABA A receptors either compensate for (1) a deficient GABAergic modulation, (2) an increase in the efficacy of excitatory inputs converging onto this structure, or (3) both. Together, these results show that the life‐long consequences of NMS are far reaching as they can compromise the development of vital homeostatic function in a way that may predispose to respiratory disorders.