Progesterone enhances motor, anxiolytic, analgesic, and antidepressive behavior of wild-type mice, but not those deficient in type 1 5 alpha-reductase.
The importance of progesterone's (P(4)) metabolism by the 5 alpha-reductase type I enzyme was examined in homozygous and heterozygous 5 alpha-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 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP) levels were determined by radioimmunoassay. Motor behavior in the horizontal crossing and open field tasks of 5 alpha-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, 5 alpha-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 5 alpha-reductase-deficient or wild-type mice significantly increased open arm activity compared to vehicle-administered control mice. P(4) to wild-type, but not 5 alpha-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, 5 alpha-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 5 alpha-reductase type I enzyme may mitigate P(4)'s effects on some tasks of motor, anxiety, nociception, and depression behavior.
Frye
Cheryl A
CA
Department of Psychology and Center for Neurobiology, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA. cafrye@cnsunix.albany.edu
Walf
Alicia A
AA
Rhodes
Madeline E
ME
Harney
Jacob P
JP
D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000201:enzymology*; D042944:Cholestenone 5 alpha-Reductase / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D003863:Depression / Q000188:drug therapy / Q000201:enzymology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011374:Progesterone / Q000494:pharmacology* / Q000627:therapeutic use
D011374:Progesterone; D042944:Cholestenone 5 alpha-Reductase