An evaluation of the mechanism by which serotonergic activation depresses respiration.
The present investigation attempted to determine if the previously reported depression of respiration by serotonergic agonists was a result of peripheral or central nervous system drug effects. Systemic administration of 5-hydroxytryptophan (5-HTP) to pargyline-treated animals and 5-methoxy-N,N-di-methyltryptophan (5-MDMT) probably depress respiration secondary to central penetration of these drugs, since: 1) adult rats with biochemical evidence of partial destruction of central serotonergic neurons after neonatal intracisternal 5,7-dihydroxytryptamine were supersensitive to the respiratory depressing effect of 5-HTP and 5-MDMT; 2) the ventilatory effect of the serotonergic agonists was not reduced by surgical deafferentiation induced by bilateral transection of the glossopharyngeal nerves; 3) after sectioning of the vagus nerve, the absolute change produced by serotonergic agonists was less; however, the relative change was unaltered; and 4) inhibition of peripheral aromatic amino acid decarboxylase by RO-4-4602 significantly blunted the respiratory depressant activity of 5-HTP observed at 15 min but not that present 30 min after 5-HTP. The present fidings thus suggest that the cenvel by the activity of central serotonergic neurons.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001545:Benserazide / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology; D002946:Cisterna Magna; D004347:Drug Interactions; D005260:Female; D005930:Glossopharyngeal Nerve / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D051381:Rats; D012119:Respiration / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D014628:Vagotomy
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D008732:Methoxydimethyltryptamines; D002245:Carbon Dioxide; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D001545:Benserazide; D006916:5-Hydroxytryptophan