The Role of 5-HT Receptor Subtypes in the Ventrolateral Orbital Cortex of 5-HT-induced Antinociception in the Rat

Neuroscience. 2008 Mar 18;152(2):487-94. doi: 10.1016/j.neuroscience.2007.09.036. Epub 2007 Sep 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Area Under Curve
  • Behavior, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Frontal Lobe / drug effects*
  • Male
  • Microinjections / methods
  • Nociceptors / physiology*
  • Pain Measurement / methods
  • Pain Threshold / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / classification*
  • Receptors, Serotonin / physiology*
  • Reflex / drug effects
  • Serotonin / pharmacology*
  • Serotonin Antagonists / administration & dosage
  • Tail / physiology
  • Time Factors


  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin