Both 5-HT(1B) and 5-HT(1F) receptors modulate c-fos expression within rat trigeminal nucleus caudalis

A possible mechanism of action of antimigraine drugs such as sumatriptan is inhibition of the trigeminovascular pathway. Sumatriptan's effects might be mediated by 5-HT(1B), 5-HT(1D) or 5-HT(1F) receptors. To establish the relative importance of these subtypes, we compared the effects of sumatriptan with those of a selective 5-HT(1F) receptor agonist (LY 344864) on c-fos protein expression in the trigeminal nucleus caudalis. c-fos expression was induced in urethane-anaesthetized rats by intracisternal capsaicin administration. Sumatriptan and LY 344864 decreased the number of capsaicin-induced c-fos-like immunoreactive cells within trigeminal nucleus caudalis (ID₅₀=0.04 and 0.6 mg kg^-1). The effect of sumatriptan, but not of LY 344864, was prevented by pretreatment with the antagonist SDZ 21-009, which displays high affinity for rat 5-HT(1B) receptors. LY 344864 appears to attenuate c-fos-like immunoreactivity via 5-HT(1F) receptors, while sumatriptan acts via 5-HT(1B) receptors. The fact that activation of 5-HT(1F) receptors is sufficient to modulate the activity of the trigeminal system suggests that this receptor may be a target for antimigraine drugs with improved safety profile. Copyright (C) 1999 Elsevier Science B.V.