Brain angiotensin and anxiety-related behavior: The transgenic rat TGR(ASrAOGEN)680

Abstract

The transgenic rat TGR(ASrAOGEN)680, characterized by a transgene-producing antisense RNA against angiotensinogen in the brain, provides an opportunity to study the behavioral effects of angiotensin. While exposed to the elevated plus-maze (EPM) and the light/dark box, TGR(ASrAOGEN)680 rats showed more signs of anxiety compared to parental Sprague–Dawley (SD) rats. In the EPM, they made fewer entries into the open arms, spent less time there and more time on the closed arms. Head dips were reduced and U-turns were increased. In the light/dark box, the latency to the first re-entry into the light compartment was higher in TGR(ASrAOGEN)680. They displayed more SAP out from the dark and a reduced number of transitions between the two compartments. In the social interaction test, active social contacts were reduced, further suggesting an anxious phenotype. Although there was no transgenic effect on distance traveled in the open field, the more anxious TGR(ASrAOGEN)680 spent less time in the inner zone. Self-grooming was increased in TGR(ASrAOGEN)680 during exposure to the EPM and the open field, but was decreased in the social interaction test. In TGR(ASrAOGEN)680, tissue content of 5-HT and its metabolite 5-HIAA was lower in the hippocampus, frontal, and parietal cortex. HIAA and 5-HIAA/5-HT ratios were reduced in the hypothalamus, striatum, and septum. In the open field, the anxiogenic effect of the 5-HT2C/1B receptor agonist mCPP (0.5–1 mg/kg IP) was more pronounced in TGR(ASrAOGEN)680. The data suggest an anxious phenotype in rats with low brain angiotensinogen, possibly related to secondary dysfunctions of the brain serotonergic system.