title: GABA representation in hypoxia sensing: a ventilatory study in the rat.
abstract: Phenibut, a nonspecific GABA derivative, is clinically used as an anxiolytic and tranquilizer in psychosomatic conditions. A GABA-ergic inhibitory pathway is engaged in respiratory control at both central and peripheral levels. However, the potential of phenibut to affect the O2-related chemoreflexes has not yet been studied. In this study we seek to determine the ventilatory responses to changes in inspired O2 content in anesthetized, spontaneously-breathing rats. Steady-state 5-min responses to 10% O2 in N2 and 100% O2 were taken in each animal before and 1 h after phenibut administration in a dose 450 mg/kg, i.p. Minute ventilation and its frequency and tidal components were obtained from the respiratory flow signal. We found that after a period of irregular extension of the respiratory cycle, phenibut stabilized resting ventilation at a lower level [20.0±3.3 (SD) vs 31.1±5.2 ml/min before phenibut; P<0.01]. The ventilatory depressant effect of phenibut was not reflected in the hypoxic response. In relative terms, this response was actually accentuated after phenibut; the peak hypoxic ventilation increased by 164% from baseline vs the 100% increase before phenibut. Regarding hyperoxia, its inhibitory effect on breathing was more expressed after phenibut. In conclusion, the GABA-mimetic phenibut did not curtail hypoxic ventilatory responsiveness, despite the presence of GABA-ergic pathways in both central and peripheral, carotid body mechanisms mediating the hypoxic chemoreflex. Thus, GABA-mediated synaptic inhibition may be elaborated in a way to sustain the primarily defensive ventilatory chemoreflex.
authors: Laboratory of Respiratory Pathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, Russia.
authors: I
authors: I
authors: Tarakanov
authors: L
authors: L
authors: Tikhomirova
authors: N
authors: N
authors: Tarasova
authors: V
authors: V
authors: Safonov
authors: M
authors: M
authors: Bialkowska
authors: M
authors: M
authors: Pokorski
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000494:pharmacology* / Q000502:physiology; D002344:Carotid Body / Q000187:drug effects*; D005260:Female; D018496:Hyperoxia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D012119:Respiration / Q000187:drug effects*; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D056152:Respiratory Rate; D013990:Tidal Volume / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D002245:Carbon Dioxide; D005680:gamma-Aminobutyric Acid; D010100:Oxygen; C008842:4-amino-3-phenylbutyric acid