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

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) gen e to examine the functional role of the AT(2) receptor in the central nervo us system (CNS), We have previously shown that AT(2)-deficient mice display ed anxiety-like behavior in comparisons with wild-type mice. In the present study, we analyzed the pain threshold, learning behavior and brain edema f ormation using the tail-flick test, the tail-pinch test, the passive avoida nce task and cold injury, respectively. In the passive avoidance task and c old injury, no differences were found between wild-type mice and AT(2)-defi cient mice. In contrast, the pain threshold was significantly lower in AT(2 )-deficient mice, compared with findings in wild-type mice. The immunohisto chemical distribution of beta-endorphin in the brain was analyzed quantitat ively in AT(2)-deficient mice and wild-type mice, using microphotometry. Th e fluorescence intensity of beta-endorphin in the arcuate nucleus of the me dial basal hypothalamus (ARC) was significantly lower in AT(2)-deficient mi ce, compared with findings in wild-type mice. We found that the AT(2) recep tor does not influence learning behavior and brain edema formation. As AT(2 )-deficient mice have increased sensitivity to pain and decreased levels of brain beta-endorphin, AT(2) receptors may perhaps mediate regulation of th e pain threshold. (C) 2000 Elsevier Science Inc. All rights reserved.