The role of 5-HT receptor subtypes in the ventrolateral orbital cortex of 5-HT-induced antinociception in the rat.
The present study examined the involvement of 5-HT in the ventrolateral orbital cortex (VLO) on descending antinociception and determined which subtypes of 5-HT receptors mediated this effect. This study focused on the effects of 5-HT microinjection in the VLO of lightly anesthetized male rats on the radiant heat-evoked tail flick (TF) reflex, as well as the influence of 5-HT(1A), 5-HT(2), 5-HT(3), and 5-HT(4) receptor subtype antagonists on the effect of 5-HT. Results showed that 5-HT microinjection (2, 5, 10 microg, in 0.5 microl) into the VLO depressed the TF reflex in a dose-dependent manner. Pretreatment with 5-HT receptor antagonists (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190), cyproheptadine hydrochloride (CPT) and 1-methyl-N-(8-methyl-8-azabicyclo[3.2.3]-oct-3-yl)-1H-indazole-3-carboxamide maleate salt (LY-278,584)), specific for 5-HT(1A), 5-HT(2) and 5-HT(3) receptors, respectively, partially reversed the 5-HT-evoked inhibition. In contrast, the 5-HT(4) receptor antagonist, 1-[2-[(methylsulfonyl)-amino]ethyl]-4-piperidinyl]methyl1-methyl-1H-indole-3-carboxylate (GR 113808), had no effect on the inhibition of 5-HT. Microinjections of NAN-190, CPT and LY-278,584 alone into the VLO had no effect on the TF reflex. These results suggest that 5-HT(1A), 5-HT(2) and 5-HT(3), but not 5-HT(4) receptors, are involved in mediating 5-HT-induced antinociception in the VLO. According to different properties and distribution patterns of the 5-HT receptor subtypes on neurons, the possible mechanism of 5-HT activation of the VLO-periaqueductal gray (PAG) descending antinociceptive pathway is discussed.
Qu
C L
CL
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, Shaanxi 710061, China.
Huo
F Q
FQ
Huang
F S
FS
Li
Y Q
YQ
Tang
J S
JS
Jia
H
H
D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005625:Frontal Lobe / Q000187:drug effects*; D008297:Male; D008845:Microinjections / Q000379:methods; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000145:classification* / Q000502:physiology*; D012018:Reflex / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000008:administration & dosage; D013623:Tail / Q000502:physiology; D013997:Time Factors
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin