Perinatal Hypoxia-Induced Impairments of Behavioral and Hormonal Stress Responses in Rats and Their Correction by a Novel GABA Derivative

Abstract

The negative long-term effects of hypoxic exposure on postnatal day 2 (human incomplete pregnancy model) on behavior (open field test) and activity of the hypothalamic-pituitary-adrenal (HPA) axis were studied in pubertal rats together with the possibility of their correction by post-hypoxic administration of a GABA derivative salifen (an adduct of γ-amino-β-phenylbutyric acid and salicylic acid). It was shown that perinatal hypoxic exposure impairs the inhibitory mechanisms in the CNS as manifested in the absence of motor activity inhibition in the open field as well as in the enhanced and prolonged stress response of the HPA axis. Post-hypoxic administration of salifen (15 mg/kg) for 14 days restored efficiently the inhibitory processes except for persistently increased hormonal stress reactivity of the HPA axis. Possible mechanisms underlying the therapeutic effects of salifen are discussed.