Central Serotonergic Modulation of Carrageenin-induced Pedal Inflammation in Rats

Putative central serotonergic modulation of acute peripheral inflammation was investigated in rats, using the carrageenin-induced pedal edema as the experimental model. Serotonin and the serotonin precursor 5-hydroxytryptophan (5HTP) produced a dose-related inhibition of the peripheral edema when given intracerebroventricularly (icv) and ip, together with the peripheral decarboxylase inhibitor benserazide. Quipazine, which inhibits neuronal release of serotonin, 5,6-dihydroxytryptamine (DHT), a specific serotonergic neurotoxin, and p-chlorphenylalanine, a selective serotonin synthesis inhibitor, augmented carrageenin inflammation upon icv administration. Metergoline, a serotonin receptor antagonist, inhibited the anti-inflammatory effect of centrally administered serotonin. However, another serotonin receptor antagonist, methysergide, produced a serotonin-like effect. The inflammation-inhibiting effect of centrally administered methysergide was antagonized after DHT-pretreatment. The findings indicate that in rats central serotonin has a modulatory inhibitory effect on acute peripheral inflammation. It was further shown that this inhibitory effect is not mediated either through activation of the peripheral sympathetic nervous system or the adrenal cortex.