Progesterone enhances motor, anxiolytic, analgesic, and antidepressive behavior of wild-type mice, but not those deficient in type 1 5α-reductase

The importance of progesterone's (P-4) metabolism by the 5alpha-reductase type I enzyme was examined in homozygous and heterozygous 5alpha-reductase type I knockout mice and their wild-type siblings. P-4 (1.0 mg) or vehicle was administered and effects on motor, anxiety, nociceptive, and depression behavior were observed. After testing, whole-brain progesterone and 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) levels were determined by radioimmunoassay. Motor behavior in the horizontal crossing and open field tasks of 5alpha-reductase-deficient mice administered P-4 was similar to vehicle control mice and significantly reduced compared to wild-type mice administered P-4. In the open field, 5alpha-reductase-deficient mice administered P-4 had a similar number of central entries as did vehicle control mice, both were lower than central entries Of P-4-administered wild-type mice. However, in the plus maze, P-4 to 5alpha-reductase-deficient or wild-type mice significantly increased open arm activity compared to vehicle-administered control mice. P-4 to wild-type, but not 5alpha-reductase-deficient mice, significantly increased latencies to lick front and back paws in response to radiant heat stimuli compared to vehicle administration to control mice. In the forced swim test, 5alpha-reductase-deficient mice administered P-4 were similar to vehicle control mice and the latency to immobility was significantly decreased, and the duration of immobility was significantly increased, compared to wild-type mice administered P-4. Thus, these data suggest metabolism by the 5alpha-reductase type I enzyme may mitigate P-4's effects on some tasks of motor, anxiety, nociception, and depression behavior. (C) 2004 Elsevier B.V. All rights reserved.