Depo-Provera effects on Wistar rat performance in the Y-maze

Okojie, A. K.; Oyekunle, O. A.

doi:10.1007/s11011-013-9460-9

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…Limiting the duration of treatment did not reduce the magnitude of the cognitive effect, as findings from Braden et al [8] were replicated. Other rodent studies have shown that long-term treatment of 17β-estradiol plus MPA led to impaired spatial memory performance, as compared to 17β-estradiol, in Ovx rats [10, 11]. Additionally, in young Ovx mice, MPA treatment reversed the cognitive benefits seen with progesterone alone [52].…”

Section: Discussionmentioning

confidence: 99%

“…Further, MPA is the only active ingredient in the contraceptive Depo Provera, and a documented case study revealed amnestic effects associated with its use [7]. In animal models, MPA has been associated with memory impairments across the adult lifespan [8–11] as well as adverse cellular effects in vitro [12–14]. Given the evidence that use of MPA in HT and contraceptives has potentially deleterious effects, it is imperative to determine an alternative progestin that is safer for women’s health, not only to prevent endometrial hyperplasia, but also to protect the brain and its function.…”

Section: Introductionmentioning

confidence: 99%

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A comparison of progestins within three classes: Differential effects on learning and memory in the aging surgically menopausal rat

Braden

Andrews

Acosta

et al. 2017

Behavioural Brain Research

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Introduction For decades, progestins have been included in hormone therapies (HT) prescribed to women to offset the risk of unopposed estrogen-induced endometrial hyperplasia. However, the potential effects on cognition of subcategories of clinically used progestins have been largely unexplored. Methods In two studies, the present investigation evaluated the cognitive effects of norethindrone acetate (NETA), levonorgestrel (LEVO), and medroxyprogesterone acetate (MPA) on the water radial-arm maze (WRAM) and Morris water maze (MM) in middle-aged ovariectomized rats. Results In Study 1, six-weeks of a high-dose NETA treatment impaired learning and delayed retention on the WRAM, and impaired reference memory on the MM. Low-dose NETA treatment impaired delayed retention on the WRAM. In Study 2, high-dose NETA treatment was reduced to four-weeks and compared to MPA and LEVO. As previously shown, MPA impaired working memory performance during the lattermost portion of testing, at the highest working memory load, impaired delayed retention on the WRAM, and impaired reference memory on the MM. NETA also impaired performance on these WRAM and MM measures. Interestingly, LEVO did not impair performance, but instead enhanced learning on the WRAM. Conclusions The current study corroborates previous evidence that the most commonly prescribed FDA-approved progestin for HT, MPA, impairs learning and memory in the ovariectomized middle-aged rat. When progestins from two different subcategories were investigated, NETA impaired learning and memory similarly to MPA, but LEVO enhanced learning. Future research is warranted to determine LEVO’s potential as an ideal progestin for optimal health in women, including for cognition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A comparison of progestins within three classes: Differential effects on learning and memory in the aging surgically menopausal rat

Braden

Andrews

Acosta

et al. 2017

Behavioural Brain Research

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“…Women that have a uterus must include a progestogen in their HT regimen to protect against endometrial hyperplasia (Smith et al, 1975 ). The most commonly prescribed progestin component of HT, and the sole hormone component of the contraceptive Depo Provera, medroxyprogesterone acetate (MPA), has been associated with memory impairments in rodent models across the adult lifespan (Braden et al, 2010 , 2011 ; Lowry et al, 2010 ; Okojie and Oyekunle, 2014 ) and adverse in vitro cellular effects (Nilsen and Brinton, 2002b ; Nilsen et al, 2006 ). There is evidence in postmenopausal women that combination HT treatment including MPA increases the risk of dementia (Shumaker et al, 2003 ; Coker et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

The GABAA antagonist bicuculline attenuates progesterone-induced memory impairments in middle-aged ovariectomized rats

Braden

Kingston

Koenig

et al. 2015

Front. Aging Neurosci.

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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 the GABAA antagonist, bicuculline. Thirteen month old rats received Ovx plus daily vehicle, progesterone, bicuculline, or progesterone+bicuculline injections beginning 2 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 6 hour delay was administered to evaluate memory retention. Progesterone-treated rats were the only group to increase working memory errors with the delay relative to baseline performance; again, 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 the 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.

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“…Some of the Women's Health Initiative and ancillary data have indicated a negative impact of combined HT as well; CEE plus MPA significantly increased dementia risk while CEE only yielded a non-significant increased risk, and CEE versus CEE plus MPA yielded different verbal memory effects [62,[78][79][80][81]. MPA impairs memory in rodent models across the adult lifespan, showing effects that are long-lasting and potentially non-reversible [82][83][84][85]. Detrimental cellular effects with MPA administration have also been observed, including exacerbation of glutamateinduced excitotoxicity, attenuation of estrogen-induced neuroprotection in hippocampal neuronal cell culture [86,87] and altered glutamic acid decarboxylase (GAD)65 þ 67 expression in the hippocampus and entorhinal cortex of middle-aged Ovx rats [82].…”

Section: Use Of Progestogensmentioning

confidence: 99%

Menopause, hormone therapy and cognition: maximizing translation from preclinical research

2021

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Menopause-associated and hormone-associated cognitive research has a rich history built from varied disciplines and species. This review discusses landmark rodent and human work addressing cognitive outcomes associated with varied experiences of menopause and hormone therapy. Critical variables in menopause and cognitive aging research are considered, including menopause etiology, background hormone milieu and parameters of exposure to estrogens and progestogens. Recent preclinical research has identified that menopause and ovarian hormone fluctuations across many neurobiological systems affect cognitive aging, mapping novel avenues for future research. Preclinical models provide insight into complex interdisciplinary relationships in a systematic and highly controlled fashion. We highlight that acknowledging the strengths and weaknesses for both preclinical and clinical research approaches is vital to accurate interpretation, optimal translation and the direction of future research. There is great value in collaboration and communication across preclinical and clinical realms, especially regarding reciprocal feedback of findings to advance preclinical models, improve experimental designs and enrich basic science translation to the clinic. In searching for biological mechanisms underlying the cognitive consequences of menopause and hormone therapies, it is noteworthy that clinical and preclinical scientists are grounded in the same fundamental goal of optimizing health outcomes for women across the lifespan.

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Depo-Provera effects on Wistar rat performance in the Y-maze

Cited by 6 publications

References 10 publications

A comparison of progestins within three classes: Differential effects on learning and memory in the aging surgically menopausal rat

A comparison of progestins within three classes: Differential effects on learning and memory in the aging surgically menopausal rat

The GABAA antagonist bicuculline attenuates progesterone-induced memory impairments in middle-aged ovariectomized rats

Menopause, hormone therapy and cognition: maximizing translation from preclinical research

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