“Tissue specific restoration of 5HT2A receptor expression in the cortex but not in the thalamus of 5HT2A KO mice rescues wild type levels of anxiety

N.V.WEISSTAUB,; M. ZHOU,; P.M CHAN,; J. GONZÁLEZ-MAESO,; C. GROSS,; R.HEN,; S.C. SEALFON,; J.A. GINGRICH

San Diego

Congreso; Society for Neuroscience 34nd Annual Meeting; 2004

Society for Neuroscience

Serotonin 2A (5HT2A) receptors are widely expressed in the CNS and modulate processes such as mood and anxiety. It has been shown that mice lacking the 5-HT2A receptor (2AKO), exhibit decrease anxiety-related behaviors.In order to understand the role of different subpopulations of 5HT2A receptors in the anxiogenic effects of serotonin (5-HT), we used a cre-lox strategy to specifically restore 5-HT2A receptor expression in two brain regions of 2AKO mice.The first line restores expression of  5HT2A receptor in the cortex (EMX1-CRE) with levels that are comparable with WT levels.The second line restores expression in the thalamus (SERT-CRE). mRNA levels indicated  the expression is rescued in some specific nucleus. We analyzed the behavior of EMX-CRE and SERT-CRE mice in different behavioral tests, in order to compare their response with WT and 2AKO mice. Although total locomotion in a novel open field (OF) was  unaltered in comparison to WT and 2AKO mice,SERT-CRE mice  spent proportionately more time and covered larger distance in the center of the arena,a behavior that resembles the low anxiety phenotype of 2AKO mice. In contrast, EMX-CRE mice exhibited WT levels of anxiety, spending less time and covering less distance in the center of the OF.The effects of both lines were confirmed in another anxiety-related paradigm. In summary, we have demonstrated a critical role of cortical 5-HT2A receptors in the modulation of the anxiety-related behavioral effects of 5-HT.The cortex is not a structure normally associated with anxiety but these findings may suggest a new avenue for understanding the role of 5-HT in anxiety disorders.