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Experiments with Nembutal-anesthetized cats, in which sodium oxybutyrate, tubocurarine, and ethyl alcohol are injected into the fourth ventricle of the brain, show that the respiratory disorders caused by sodium oxybutyrate or ethyl alcohol can be eliminated by tubocurarine. By blocking the central N-cholinergic receptors, tubocurarine abolishes the inhibition of respiratory movements induced through activation of the GABA-ergic system. Key Words: cholinergic system; regulation of respiration; sodium oxybutyrate; tubocurarine; ethanol; GABA The relatively high concentration of gamma-butyric acid (GABA) found at the respiratory center [2,12] and its pronounced inhibitory effects following systemic or central administration to warmblooded animals indicate that GABA participates in the regulation of respiration [3][4][5]10]. The inhibition of respiratory activity by ethanol is also believed to involve the GABA-ergic system [9]. The N-cholinergic system, too, takes part in the regulation of respiration, as is evidenced by the presence of Ncholinergic receptors in central structures of the respiratory apparatus, by the relationship of these receptors to GABA-ergic neurons, and by their strong inhibitory influence on respiration when these neurons are activated [4,10,11]. However, the involvement of the GABA-ergic system in the regulation of respiration in comparison with that of the cholinergic system remains unexplored.This study was undertaken to examine the role of the central N-cholinergic receptors in prevent- MATERIALS AND METHODSThe study was conducted on 53 tracheotomized cats (body weight 2.5-3.5 kg) under Nembutal anesthesia (40 mg/kg intraperitoneaUy). Respiratory rate, minute volume (MV), arterial pressure, and heart rate were recorded and averaged using a surgical monitor. Parameters of systemic hemodynamics were registered by means of a catheter inserted into the femoral artery. Respiratory volume was calculated as the ratio of MV to respiratory rate. Electromyograms of the phrenic muscle were taken with an M-42 electromyograph (Hungary) using bipolar metal electrodes. The GABA-ergic system was activated with sodium oxybutyrate. Oxybutyrate at 60 or 180 ~tmol/kg, tubocurarine at 130 or 300 nmol/kg, and 96% ethanol at 330 nmol/kg were injected into the fourth ventricle of the brain in a volume of 50 (the oxybutyrate and tubocurarine were dissoNed in isotonic NaCI solution and 48% ethanol, respectively). Control cats received isotonic NaC1 solution and 48% alcohol in the same volume.

In experiments with Nembutal-anesthetized cats, in which lobeline, picrotoxin, tubocurarine, and naloxone were injected into the fourth brain ventricle, respiratory disturbances resulting from activation of the central N-cholinergic receptors by lobeline injected when central GABA A receptors were blocked by picrotoxin led to respiration of the gasping type. After naloxone was administered additionally, the normal rhythmic pattern of breathing was restored.Key Words: regulation of respiration; lobeline; picrotoxin; tubocurarine; naloxone; GABAergic and cholinergic systems Blockade of the central N-cholinergic receptors with tubocurarine has been shown to abolish the inhibition of respiratory activity caused by sodium oxybutyrate (or by ethanol), indicating that the cholinergic system is actively involved in the regulation of respiration [2]. It has also been found that N-cholinergic receptors exist at the respiratory center and that GABA-ergic and cholinergic neurons are sequentially linked in certain brain regions [4,9,[11][12][13].The present study was designed to explore the interrelationship between the central N-cholinergic and GABA receptors during the formation of the respiratory rhythm and, in particular, the development of terminal respiration. MATERIALS AND METHODSThe study was conducted on 68 cats (body weight 2.5-4.0 kg) under Nembutal anesthesia (40 mg/kg intraperitoneally) [21. Lobeline at 800 nmol/kg or 3-4 gmol/kg, picrotoxin at 30 nmol/kg, tubocurarine at 130 nmol/kg, and naloxone at 20 nmol/kg were injected into the fourth ventricle of the brain in a volume of 50 p.1 (lobeline and naloxone in isotonic NaC1 solution and picrotoxin and tubocurarine in 48% ethanol). In control tests, isotonic NaC1 solution and 48% ethanol were similarly administered in the same volume as above (the effects from control injections are described in the preceding article [2]). Preliminarily, the carotid nerves were cut to denervate the carotid sinuses and thus prevent the respiratory effect of lobeline on the peripheral N-cholinergic receptors of carotid body cells. The cats were tracheotomized in order to record respiratory parameters and institute artificial ventilation. RESULTSIn tests on 10 cats, designed to see how lobeline would affect respiration under normal conditions, injection of this drag at 800 nmol/kg was followed within 1 min by a sharp decrease in minute volume (MV) as a result of falls in both respiratory rate and respiratory volume, to the point of respiratory arrest for 10-15 min (the cats were on artificial ventilation during that period); 50 to 60 min after lobeline injection, spontaneous respiratory movements were restored and the respiratory rate and volume reached their baseline values (Fig.