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Affect-related behaviors in mice misexpressing the RNA editing enzyme ADAR2
Journal article   Open access   Peer reviewed

Affect-related behaviors in mice misexpressing the RNA editing enzyme ADAR2

Minati Singh, M Bridget Zimmerman, Terry G Beltz and Alan Kim Johnson
Physiology & behavior, Vol.97(3-4), pp.446-454
06/22/2009
DOI: 10.1016/j.physbeh.2009.03.029
PMCID: PMC2778280
PMID: 19361536
url
http://doi.org/10.1016/j.physbeh.2009.03.029View
Open Access

Abstract

Misediting of the serotonin (5HT) 2C receptor (5HT(2C)R) has been implicated in both depression and anxiety. The adenosine deaminases that act on double stranded RNAs (ADARs) are reported to modify the 5HT(2C)R by RNA editing. Transgenic mice misexpressing the RNA editing enzyme ADAR2 show an adult onset obese phenotype due to chronic hyperphagia, but little more than this is known about the behavior of these animals. The present experiments examined whether affect-associated behaviors are also altered in ADAR2 transgenic mice. Age- and weight-matched transgenic mice misexpressing ADAR2 were tested for signs of behavioral despair with the forced swim (FST) and tail suspension (TST) tests, and for anxiety by evaluating spontaneous exploration in a novel environment and by elevated plus maze performance. Plasma corticosterone was also determined by radioimmunoassay. Transgenic mice of both sexes displayed indications of increased behavioral despair on first exposures to the TST and the FST. Behavioral despair persisted in ADAR2 mice in that it was also observed in the FST in tests administered 24 h and 1 week following the initial TST and FST. ADAR2 transgenic mice also displayed behaviors associated with anxiety as indicated by decreased entry into the open arms in an elevated plus maze test. Both sexes of ADAR2 transgenic mice displayed elevated plasma corticosterone. Taken together, the results suggest that ADAR2 transgenic mice represent a novel rodent model of endogenous behavioral despair and anxiety accompanied by elevated hypothalamo-pituitary adrenal axis activity.
Maze Learning - physiology Adenosine Deaminase - genetics RNA Editing - genetics Mice, Inbred C57BL Genotype Male Mice, Transgenic RNA-Binding Proteins Hindlimb Suspension - methods Body Weight - genetics Affective Symptoms - genetics Behavior, Animal Swimming - physiology Exploratory Behavior - physiology Motor Activity - genetics Animals Analysis of Variance Female Mice Affective Symptoms - blood Affective Symptoms - physiopathology Corticosterone - blood Disease Models, Animal

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