BRAIN METABOLISM OF PROGESTERONE, COPING BEHAVIOR AND EMOTIONAL REACTIVITY IN MALE-RATS FROM 2 PSYCHOGENETICALLY SELECTED LINES

Brain metabolites of progesterone such as tetrahydroprogesterone (THP) act on GABA, receptors and have anxiolytic properties. The formation of THP and its 5 alpha-reduced precursor, dihydroprogestrone (DHP) was measured in vitro in various microdissected brain areas obtained from males of two psychogenetically selected rat lines, i.e. the Roman Hig h-(RHA/Verh) and Low-(RLA/Verh) Avoidance rats, which are known to dif fer in emotional reactivity and/or anxiety. The behavioural and neuroe ndocrine responses of these rats were also measured following exposure to a novel environment in two different test situations. The formatio n of DHP and THP was found to be significantly higher in the frontal c ortex (FCX), and DHP in the bed nucleus of the stria terminalis (BST), of the hypoemotional RHA/Verh rats. In addition, enzymatic activity i n the FCX was found to be inversely correlated with behavioural measur es of anxiety. These results suggest that individual, possibly genetic ally-determined differences in brain production of endogenous anxiolyt ics derived from progesterone may account at least in part for the beh avioural differences characterizing these two lines, and provide furth er evidence that neurosteroids acting on the GABAergic system may play an important role in modulating physiological and/or behavioural resp onses to environmental stressors.