The anxiolytic-like effects of allopregnanolone vary as a function of intracerebral microinfusion site: the amygdala, medial prefrontal cortex, or hippocampus.

Abstract

Allopregnanolone is a 5alpha-reduced metabolite of progesterone that potentiates gamma-aminobutyric acid type-A (GABA(A)) receptor activity and produces anxiolytic effects in animal models. Little is, however, known about the brain regions that mediate its anxiolytic effects. In this study Sprague-Dawley rats were microinfused with allopregnanolone into the amygdala, medial prefrontal cortex, or hippocampus--brain regions that have been previously implicated in the control of anxiety in animal models. After the microinfusion, the animals were tested on the elevated plus-maze and the shock-probe burying test. In the amygdala, allopregnanolone produced anxiolytic-like effects in both tests; in the medial prefrontal cortex, allopregnanolone produced anxiolytic effects restricted to the plus-maze test; in the hippocampus, allopregnanolone was ineffective in both tests. The results were discussed in terms of differences in the control of specific fear reactions within subregions of each brain area, differences in the 'sensitivity' of behavioral tests to the anxiolytic effects of allopregnanolone, and finally, regional differences in the subunit composition of GABA(A) receptors and their possible relationship to the relative efficacy of steroidal and nonsteroidal GABA(A) agonists.