Activation of serotonin 1A receptors in ventrolateral orbital cortex depresses persistent nociception: A presynaptic inhibition mechanism

The present study examined the effect of serotonin 1A (5-HT1A) receptor activation in the ventrolateral orbital cortex (VLO) upon formalin-evoked flinching behavior and spinal Fos expression, and further determined whether activation of 5-HT1A receptors affected the spontaneous GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in rat VLO slice by pharmacologically separated neurons to understand the possible mechanism underlying this effect. Microinjection of the 5-HT1A receptors agonist 8-OH-DPAT (8-hydro-2-(di-n-propylamino) tetralin) into the VLO depressed the formalin-evoked nociceptive behavior flinching response and the Fos expression in the lumbar spinal cord dorsal, which was antagonized by pre-treatment with 5-HT1A receptors antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide). Furthermore, application of 8-OH-DPAT into VLO slice inhibited GABAergic mIPSC frequency in a dose-dependent manner without effects on amplitude of the GABAergic mIPSCs, this effect was blocked by NAN-190. These results provide evidence for the involvement of 5-HT1A receptors in VLO in the modulation of persistent inflammatory nociception, and suggest that a presynaptic inhibition of the GABA release may contribute to the 5-HT1A receptor-mediated descending antinociception.

Research highlights▶ Activation of the VLO 5-HT1A receptor inhibits formalin-evoked nociceptive behavior. ▶ Activation of the VLO 5-HT1A receptor inhibits formalin-evoked spinal Fos expression. ▶ Antinociception is produced by 5-HT1A receptor presynaptic inhibiting GABA release.