GABAergic inhibition of hiccup-like reflex induced by electrical stimulation in medulla of cats

Abstract

We hypothesize that the hiccup reflex is actively inhibited through GABA B receptor within central connections of the hiccup reflex arc. Because the hiccup-like reflex can be elicited by electrical stimulation to a limited area within the medullary reticular formation, the hiccup-evoking site (HES), electrical stimulation (50–100 μA, three train pulses at 20 Hz) was delivered to HES by means of a metal electrode containing 1.0 mM baclofen, in anesthetized spontaneously breathing cats. The evoked response was characterized by a brief powerful increase in diaphragmatic activity and a temporal suppression of the posterior cricoarytenoid muscle, laryngeal dilator, which corresponded to the fixed motor pattern of hiccup reflex. The hiccup-like response was rapidly suppressed after microinjection of baclofen (0.1–0.5 nmol) into HES, indicating that HES has GABA B receptors. In the other experiments, to histologically examine the inputs to the hiccup reflex arc, unconjugated cholera toxin subunit B (UCTB) was injected into HES. Following injections of UCTB, retrogradely labelled cells were found distributed in various areas of the lower brainstem. Among these areas, the nucleus raphe magnus (RM) is reported to have GABA-containing cells. It is thus hypothesized that RM is most likely to be the source of the GABAergic inhibitory inputs to the hiccup reflex arc.