Pain threshold, learning and formation of brain edema in mice lacking the angiotensin II type 2 receptor

Abstract The main biological role of angiotensin II type 2 receptor (AT 2 ) has not been established. We made use of targeted disruption of the mouse AT 2 gene to examine the functional role of the AT 2 receptor in the central nervous system (CNS). We have previously shown that AT 2 -deficient mice displayed anxiety-like behavior in comparisons with wild-type mice. In the present study, we analyzed the pain threshold, learning behavior and brain edema formation using the tail-flick test, the tail-pinch test, the passive avoidance task and cold injury, respectively. In the passive avoidance task and cold injury, no differences were found between wild-type mice and AT 2 -deficient mice. In contrast, the pain threshold was significantly lower in AT 2 -deficient mice, compared with findings in wild-type mice. The immunohistochemical distribution of β-endorphin in the brain was analyzed quantitatively in AT 2 -deficient mice and wild-type mice, using microphotometry. The fluorescence intensity of β-endorphin in the arcuate nucleus of the medial basal hypothalamus (ARC) was significantly lower in AT 2 -deficient mice, compared with findings in wild-type mice. We found that the AT 2 receptor does not influence learning behavior and brain edema formation. As AT 2 -deficient mice have increased sensitivity to pain and decreased levels of brain β-endorphin, AT 2 receptors may perhaps mediate regulation of the pain threshold.