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-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.
Huo
Fu-Quan
FQ
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.
Huang
Fen-Sheng
FS
Lv
Bo-Chang
BC
Chen
Tao
T
Feng
Jie
J
Qu
Chao-Ling
CL
Tang
Jing-Shi
JS
Li
Yun-Qing
YQ
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
D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin