TY - JOUR
T1 - The GABAA antagonist bicuculline attenuates progesterone-induced memory impairments in middle-aged ovariectomized rats
AU - Braden, Brittany
AU - Kingston, Melissa L.
AU - Whitton, Elizabeth
AU - Lavery, Courtney
AU - Tsang, Candy W S
AU - Bimonte-Nelson, Heather
N1 - Publisher Copyright:
© 2015 Braden, Kingston, Whitton, Lavery, Tsang and Bimontenelson.
PY - 2015
Y1 - 2015
N2 - In women, high levels of natural progesterone have been associated with detrimental cognitive effects via the "maternal amnesia" phenomenon as well as in controlled experiments. In aged ovariectomized (Ovx) rats, progesterone has been shown to impair cognition and impact the GABAergic system in cognitive brain regions. Here, we tested whether the GABAergic system is a mechanism of progesterone's detrimental cognitive effects in the Ovx rat by attempting to reverse progesterone-induced impairments via concomitant treatment with GABAA antagonist, bicuculline. Thirteen month old rats received Ovx plus daily vehicle, progesterone, bicuculline, or progesterone+bicuculline injections beginning two weeks prior to testing. The water radial-arm maze was used to evaluate spatial working and reference memory. During learning, rats administered progesterone made more working memory errors than those administered vehicle, and this impairment was reversed by the addition of bicuculline. The progesterone impairment was transient and all animals performed similarly by the end of regular testing. On the last day of testing, a six hour delay was administered to evaluate memory retention. Progesterone-treated rats were the only group to increase working memory errors with the delay; the addition of bicuculline prevented the progesterone-induced impairment. The vehicle, bicuculline, and progesterone+bicuculline groups were not impaired by the delay. The current rodent findings corroborate prior research reporting progesterone-induced detriments on cognition in women and in the aging Ovx rat. Moreover, the data suggest that progesterone-induced cognitive impairment is, in part, related to the GABAergic system. Given that progesterone is included in numerous clinically-prescribed hormone therapies and contraceptives (e.g. micronized), and as synthetic analogs, further research is warranted to better understand the parameters and mechanism(s) of progesterone-induced cognitive impairments.
AB - In women, high levels of natural progesterone have been associated with detrimental cognitive effects via the "maternal amnesia" phenomenon as well as in controlled experiments. In aged ovariectomized (Ovx) rats, progesterone has been shown to impair cognition and impact the GABAergic system in cognitive brain regions. Here, we tested whether the GABAergic system is a mechanism of progesterone's detrimental cognitive effects in the Ovx rat by attempting to reverse progesterone-induced impairments via concomitant treatment with GABAA antagonist, bicuculline. Thirteen month old rats received Ovx plus daily vehicle, progesterone, bicuculline, or progesterone+bicuculline injections beginning two weeks prior to testing. The water radial-arm maze was used to evaluate spatial working and reference memory. During learning, rats administered progesterone made more working memory errors than those administered vehicle, and this impairment was reversed by the addition of bicuculline. The progesterone impairment was transient and all animals performed similarly by the end of regular testing. On the last day of testing, a six hour delay was administered to evaluate memory retention. Progesterone-treated rats were the only group to increase working memory errors with the delay; the addition of bicuculline prevented the progesterone-induced impairment. The vehicle, bicuculline, and progesterone+bicuculline groups were not impaired by the delay. The current rodent findings corroborate prior research reporting progesterone-induced detriments on cognition in women and in the aging Ovx rat. Moreover, the data suggest that progesterone-induced cognitive impairment is, in part, related to the GABAergic system. Given that progesterone is included in numerous clinically-prescribed hormone therapies and contraceptives (e.g. micronized), and as synthetic analogs, further research is warranted to better understand the parameters and mechanism(s) of progesterone-induced cognitive impairments.
KW - Aging
KW - Bicuculine
KW - Gaba
KW - Hormone therapy
KW - Memory
KW - Menopause
KW - Progesterone
UR - http://www.scopus.com/inward/record.url?scp=84938594163&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938594163&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2015.00149
DO - 10.3389/fnagi.2015.00149
M3 - Article
AN - SCOPUS:84938594163
SN - 1663-4365
VL - 7
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
IS - JUL
M1 - 149
ER -