Anxiolytic effects of 5-HT₁A receptors and anxiogenic effects of 5-HT₂C receptors in the amygdala of mice

Neuropharmacology. 2012 Jan;62(1):474-84. doi: 10.1016/j.neuropharm.2011.09.002. Epub 2011 Sep 14.

Abstract

The aim of the present study is to test a hypothesis that 5-HT(1A) and 5-HT(2C) receptors in the amygdala play an important role in the regulation of anxiety behaviors. We examined alterations in anxiety-like behaviors after manipulation of the expression of 5-HT(1A) and 5-HT(2C) receptors in the amygdala using recombinant adenovirus approaches. Recombinant adenoviruses containing a 5-HT(1A) promoter-controlled 5-HT(1A) antisense sequence or a 5-HT(2C) promoter-controlled 5-HT(2C) sense sequence were injected into the amygdala. Elevated plus-maze (EPM) and open field tests were conducted to determine anxiety-like behavior and locomotor activity. Reductions in the expression of 5-HT(1A) receptors in the amygdala significantly attenuated the time spent in the open arms of EPM and time spent in the center of an open field. Reduction in the percent of time spent in the open arms of EPM is negatively correlated with the density of 5-HT(1A) receptors in the central amygdala. On the other hand, increased expression of 5-HT(2C) receptors reduced the time spent in the open arms of EPM and time spent in the center of an open field. The reductions in the time spent and distance traveled in the open arms of EPM were correlated to the density of 5-HT(2C) receptors in the basolateral nucleus of amygdala. These data suggest that amygdaloid 5-HT(1A) receptors produce anxiolytic and 5-HT(2C) receptors produce anxiogenic effects. Together, the present results demonstrate the important role of the amygdaloid 5-HT(1A) and 5-HT(2C) receptors in the regulation of anxiety-like behaviors. This article is part of a Special Issue entitled 'Anxiety and Depression'.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Aminopyridines / pharmacokinetics
  • Amphetamines / pharmacokinetics
  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Analysis of Variance
  • Animals
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / pharmacology
  • Anxiety / drug therapy
  • Anxiety / metabolism*
  • Anxiety / pathology*
  • Autoradiography
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Genetic Vectors / physiology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Iodine Radioisotopes / pharmacokinetics
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Oligodeoxyribonucleotides, Antisense / administration & dosage
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Piperazines / pharmacokinetics
  • Protein Binding / drug effects
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Serotonin Antagonists / pharmacokinetics
  • Serotonin Receptor Agonists / pharmacokinetics
  • Time Factors

Substances

  • Aminopyridines
  • Amphetamines
  • Anti-Anxiety Agents
  • Iodine Radioisotopes
  • Oligodeoxyribonucleotides, Antisense
  • Piperazines
  • Receptor, Serotonin, 5-HT2C
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • Green Fluorescent Proteins
  • 4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine
  • 4-iodo-2,5-dimethoxyphenylisopropylamine