title: Activation of serotonin 1A receptors in ventrolateral orbital cortex depresses persistent nociception: a presynaptic inhibition mechanism.
abstract: The present study examined the effect of serotonin 1A (5-HT(1A)) receptor activation in the ventrolateral orbital cortex (VLO) upon formalin-evoked flinching behavior and spinal Fos expression, and further determined whether activation of 5-HT(1A) 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-HT(1A) 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-HT(1A) 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-HT(1A) 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-HT(1A) receptor-mediated descending antinociception.
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, China.
authors.forename: Fu-Quan
authors.initials: FQ
authors.lastname: Huo
authors.forename: Fen-Sheng
authors.initials: FS
authors.lastname: Huang
authors.forename: Bo-Chang
authors.initials: BC
authors.lastname: Lv
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.forename: Chao-Ling
authors.initials: CL
authors.lastname: Qu
authors.forename: Jing-Shi
authors.initials: JS
authors.lastname: Tang
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin