BEHAVIORAL REACTIVITY TO AVERSIVE STIMULI IN A TRANSGENIC MOUSE MODELOF IMPAIRED GLUCOCORTICOID (TYPE-II) RECEPTOR FUNCTION - EFFECTS OF DIAZEPAM AND FG-7142

Transgenic mice with impaired type II-glucocorticoid receptor mediated feedback inhibition of hypthalamic-pituitary-adrenal activity were as sessed in three different tests assessing behavioral reactivity to ave rsive stimuli, the elevated plus maze, the Thatcher-Britton novelty-co nflict paradigm, and the startle paradigm. Transgenic mice more freque ntly entered and spent more time in the open arms of the elevated plus in comparison to B6C/3F1 mice. Transgenic mice took significantly lon ger to begin eating in the Thatcher-Britton novelty conflict paradigm, and displayed increased reactivity in the startle paradigm. Administr ation of 1 or 2 mg/kg diazepam reversed the behavioral effects observe d in all three tests. Administration of the benzodiazepine receptor in verse agonist N-methyl-beta-carboline-3 carboxamide (FG-7142, 10 mg/kg ) reduced the ratio of open to total arm entries and the time spent in the open arms of the plus maze in transgenic, but not B6C/3F1, mice. This dose of FG-7142 did not influence performance of either strain in the Thatcher-Britton or startle paradigms. These results are discusse d in terms of the hypothesis that the transgenic mice are more sensiti ve to the aversive properties of novel stimuli, and that they may have difficulty discriminating between signals of relative safety and dang er.