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

Abstract

The aim of the present study is to test a hypothesis that 5-HT1A and 5-HT2C 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-HT1A and 5-HT2C receptors in the amygdala using recombinant adenovirus approaches. Recombinant adenoviruses containing a 5-HT1A promoter-controlled 5-HT1A antisense sequence or a 5-HT2C promoter-controlled 5-HT2C 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-HT1A 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-HT1A receptors in the central amygdala. On the other hand, increased expression of 5-HT2C 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-HT2C receptors in the basolateral nucleus of amygdala. These data suggest that amygdaloid 5-HT1A receptors produce anxiolytic and 5-HT2C receptors produce anxiogenic effects. Together, the present results demonstrate the important role of the amygdaloid 5-HT1A and 5-HT2C receptors in the regulation of anxiety-like behaviors.