Reduced Progesterone Metabolites Are Not Critical for Plus-Maze Performance of Lactating Female Rats

Lactation has been associated with anxiolysis in several tests of anxiety. These observations, considered together with observations that progesterone and its 5 alpha-reduced metabolites are anxiolytic in cycling, nonlactating females, raised the question of whether the changes in anxiety-related behaviors that accompany lactation are driven by reduced progesterone metabolites. Lactating female rats were tested on the plus-maze on postpartum days 2 or 7, and demonstrated enhanced open-arm performance relative to cycling, nonlactating females. Hormonal analysis indicated that while serum levels of both progesterone and its 3 alpha,5 alpha-reduced metabolite were increased in lactating females, the turnover of progesterone to the metabolite was markedly reduced during lactation. Further more, treatment with a 5 alpha-reductase inhibitor for 3 days prior to testing potentiated the open-arm performance in lactating females, implying that enhanced open-arm performance was not mediated by the reduction of progesterone or other steroids. Additionally, analysis of GABAA receptor function indicated that parturition and lactation did not alter the sensitivity of the receptor to GABA or to modulation by reduced steroids. The mechanisms driving enhanced plus-maze behavior in lactating females appear to differ from mechanisms identified in nonlactating females. (C) 1999 Elsevier Science Inc.