TY - JOUR
T1 - Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility
AU - Beckley, Ethan H.
AU - Finn, Deborah A.
N1 - Funding Information:
This work was supported by National Institutes of Health grants AA10760 and AA12439, and a Merit Award from the Department of Veterans affairs (D. A. F.). E. H. B. was also supported by the NIH training grant T32-AA07468 (awarded to Dr. Christopher L. Cunningham), and by the Nancy and Dodd Fischer Scholarship, administered by the Portland, OR chapter of the ARCS Foundation. Drs. Suzanne H. Mitchell and John C. Crabbe and two anonymous faculty members provided valuable feedback on some of the work reported herein. Drs. James J. Crowley and Irwin Lucki provided expert information on the technical parameters for the forced swim test. Ms. Andrea Fretwell provided invaluable assistance with animal care.
PY - 2007/10
Y1 - 2007/10
N2 - Withdrawal from high levels of progesterone in rodents has been proposed as a model for premenstrual syndrome or postpartum depression. Forced swim test (FST) immobility, used to model depression, was assessed in intact female DBA/2J mice following progesterone withdrawal (PWD) or treatment with the 5α-reductase inhibitor finasteride. Following 5 daily progesterone injections (5 mg/kg IP) FST immobility increased only in mice withdrawn for 3 days (p < .05). In another experiment, 3 days of PWD significantly decreased levels of progesterone compared to 0 days of withdrawal, but progesterone levels at 3 days of PWD did not differ from vehicle-treated controls. In a final study, mice received daily injections of progesterone (5 mg/kg IP) for 8 days, with 0 mg/kg, 50 mg/kg, or 100 mg/kg finasteride co-administered for the last three days. Mice that received 100 mg/kg finasteride, but not 50 mg/kg finasteride, displayed increased FST immobility. PWD and finasteride treatment, both of which reduce allopregnanolone levels, were associated with increased FST immobility in female DBA/2J mice. These findings suggest that decreased levels of the GABAergic neurosteroid allopregnanolone contribute to symptoms of PWD. Future studies of PWD may provide information about human conditions that are associated with hormone changes such as premenstrual syndrome or postpartum depression.
AB - Withdrawal from high levels of progesterone in rodents has been proposed as a model for premenstrual syndrome or postpartum depression. Forced swim test (FST) immobility, used to model depression, was assessed in intact female DBA/2J mice following progesterone withdrawal (PWD) or treatment with the 5α-reductase inhibitor finasteride. Following 5 daily progesterone injections (5 mg/kg IP) FST immobility increased only in mice withdrawn for 3 days (p < .05). In another experiment, 3 days of PWD significantly decreased levels of progesterone compared to 0 days of withdrawal, but progesterone levels at 3 days of PWD did not differ from vehicle-treated controls. In a final study, mice received daily injections of progesterone (5 mg/kg IP) for 8 days, with 0 mg/kg, 50 mg/kg, or 100 mg/kg finasteride co-administered for the last three days. Mice that received 100 mg/kg finasteride, but not 50 mg/kg finasteride, displayed increased FST immobility. PWD and finasteride treatment, both of which reduce allopregnanolone levels, were associated with increased FST immobility in female DBA/2J mice. These findings suggest that decreased levels of the GABAergic neurosteroid allopregnanolone contribute to symptoms of PWD. Future studies of PWD may provide information about human conditions that are associated with hormone changes such as premenstrual syndrome or postpartum depression.
KW - Allopregnanolone
KW - Behavioral despair
KW - Depression
KW - Finasteride
KW - GABA-A receptor
KW - Postpartum depression
KW - Premenstrual syndrome
KW - Progesterone withdrawal
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U2 - 10.1016/j.pbb.2007.05.017
DO - 10.1016/j.pbb.2007.05.017
M3 - Article
C2 - 17597197
AN - SCOPUS:34547838202
SN - 0091-3057
VL - 87
SP - 412
EP - 419
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 4
ER -