Excitotoxic lesions of the medial prefrontal cortex attenuate fear responses in the elevated-plus maze, social interaction and shock probe burying tests

Abstract

Previous research investigating the effects of medial prefrontal cortex (MPFC) lesions on fear- and anxiety-related behavior has yielded an inconsistent body of findings. Behavioral studies have reported increases, decreases, and no effect on anxiety. In addition, many studies are complicated by the use of lesioning techniques that destroy fibers of passage, and the use of conditioned fear tests, which may introduce the confounding effects of learning and memory. Therefore, the present study examined the effects of ibotenic acid lesions of the MPFC (including prelimbic, infralimbic and anterior cingulate) on three wide-ranging and well-validated behavioral assays of anxiety: the elevated plus maze (EPM), social interaction (SI) and the shock-probe tests (SP). In the EPM test, lesioned rats showed a significantly higher percentage of open arm entries and open arm time than controls. In a version of the SI test sensitive to anxiolytic effects, lesioned rats were found to spend a significantly greater amount of time in active interaction with a conspecific; while another version of the SI test sensitive to anxiogenic effects did not show any differences between lesioned and non-lesioned controls. In the SP test, lesioned rats exhibited significantly lower rates of burying. In contrast, retention of shock probe avoidance was not affected. No effects of lesions on measures of locomotor activity or shock reactivity were found. The concordant anxiolytic-like effects found in the three behavioral assays strongly suggests a general reduction in fear responsiveness in MPFC lesioned rats.