Changes in serotonin metabolism may elicit obstructive apnoea in the newborn rat.
1. Experiments were performed on anaesthetized newborn rats (aged 3-10 days) to know whether an increase in central serotonin levels might favour the occurrence of obstructive apnoeas as previously suggested by in vitro results from our group. 2. The levels of serotonin (5-HT), its precursor 5-hydroxytryptophan (5-HTP) and its metabolite, 5-hydroxyindole-acetic acid (5-HIAA), were analysed in cerebrospinal fluid samples collected at the level of the obex prior to and after intraperitoneal injection of L-tryptophan (50 mg kg-1) in sixty-eight anaesthetized newborn rats (control rats prior to injection and injected rats 15, 30 and 45 min after the injection). A significant increase in 5-HT and 5-HTP levels occurred 30 min after the injection, attesting to the activation of 5-HT biosynthesis. 3. The EMG activity of both the genioglossus and the diaphragm was recorded before and after L-tryptophan load (50 mg kg-1) in twenty-two newborn rats. After the injection of L-tryptophan, the amplitude of the integrated genioglossus activity decreased, or was even abolished, either during a few respiratory cycles or for long periods in twenty-one out of twenty-two animals. Recovery of the genioglossus activity occurred within 45-60 min. 4. The thoracic respiratory movements and the resulting upper airway pressure changes were recorded before and after L-tryptophan injection (50 mg kg-1) in sixty-two animals. In some litters (n = 7), most of the animals (21/25) displayed, within 20-40 min of the injection, recurrent episodes of obstructive apnoea often followed by central ones. These respiratory difficulties became severe and drastic, and led in two instances to respiratory distress and death. Lower doses of L-tryptophan (10 mg kg-1) did not induce any respiratory disorders unless these were potentiated by pargyline treatment (50 mg kg-1, n = 7). The obstructive apnoeas liable to occur after an L-tryptophan load (50 mg kg-1) were prevented by blocking the 5-HT receptor with methysergide (50 mg kg-1, n = 5) or by blocking the 5-HT biosynthesis by applying p-chlorophenylalanine (PCPA) pretreatment at birth (300 mg kg-1, n = 7). In other litters (n = 6), none of the eighteen newborn rats tested were affected by L-tryptophan, however, In five young adult rats, L-tryptophan again had no effect.4+ ĕ
Hilaire
G
G
Equipe Biologie des Rythmes et du Développement, URA CNRS 0205, Faculté des Sciences et Techniques St-Jérôme, Marseille, France.
Morin
D
D
Lajard
A M
AM
Monteau
R
R
D006916:5-Hydroxytryptophan / Q000134:cerebrospinal fluid; D000818:Animals; D000831:Animals, Newborn; D004576:Electromyography; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D007223:Infant; D007274:Injections, Intraperitoneal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012132:Respiratory Muscles / Q000187:drug effects / Q000503:physiopathology; D012701:Serotonin / Q000134:cerebrospinal fluid / Q000378:metabolism*; D012891:Sleep Apnea Syndromes / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000503:physiopathology; D013398:Sudden Infant Death / Q000209:etiology; D014364:Tryptophan / Q000008:administration & dosage
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D006916:5-Hydroxytryptophan