Serotoninergic and suprachiasmatic nucleus involvement in the corticotropic response to systemic endotoxin challenge in rats

We have investigated whether the serotonin system participates in the mecha nisms underlying the corticotropic response in experimentally infected rats . Intra-arterial injection of lipopolysaccharide (LPS; 25 mu g/kg b.w.) res ulted in a slight but significant increase in serotonin (5-HT) metabolism, detectable 60 min after the stimulus and lasting more than 480 min. Adrenoc orticotropin (ACTH) and corticosterone (CORT) responses in intact rats conf ormed to earlier reports, increasing as early as 30 min after LPS injection and reaching maximal concentrations in the circulation 60 min after the ba cterial endotoxin injection. Plasma concentrations of interleukin-1 beta (I L-1 beta) increased only after 60 min, reaching maximal levels 120 min afte r LPS, Depletion of hypothalamic 5-HT (-93%) by pretreatment of the animals with para-chlorophenylalanine (p-CPA), resulted in a halved ACTH response to LPS, despite an overall unchanged secretory pattern, Neither CORT nor IL -1 beta secretory patterns were affected in these rats pretreated with p-CP A. Complete bilateral electrochemical lesions of the suprachiasmatic nucleu s (SCN), which is innervated by mesencephalic 5-HT, impaired the early phas e of the ACTH (-75% at 30 min) and CORT (-40% at 30 min) responses but did not affect the later increases of the corticotropic and the plasma IL-1 bet a responses following the LPS injection. These results indicate that seroto nin pathways and SCN are involved in the earlier mechanisms of corticotropi c axis recruitment following systemic LPS endotoxemia.