Administration of an inhibitor of estrogen biosynthesis facilitates working memory acquisition in male rats

Alejandre-Gómez, Misael; Garcia-Segura, Luis Miguel; González-Burgos, Ignacio

doi:10.1016/j.neures.2007.03.011

Cited by 40 publications

(34 citation statements)

References 52 publications

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“…Moreover, the effect of LTZ appears to be due to the impact of E2 synthesis inhibition on the plasticity of the visuo-vestibular network since no changes were found in basal optokinetic and vestibular reflexes after LTZ administration. In support of these data, it has been shown that inhibiting E2 synthesis using a dose of aromatase imidazole derivative inhibitors similar to the one used in this study, can rapidly affect the adaptive behavior of rodents (Alejandre-Gomez et al 2007;Graham and Milad 2014;Taziaux et al 2007). In addition, the effect of the LTZ timescale observed in our behavioral experiments is supported by pharmacokinetic results showing that in male rat brain tissue, LTZ reaches high concentration in less than 3 h after a single oral dose (2-3.6 mg/kg) with apparent terminal half-life around 12 h and is completely eliminated from the blood within 36 h (Liu et al 2000;Wempe et al 2007).…”

Section: Neurosteroid E2 Is Necessary For Vor Adaptationsupporting

confidence: 77%

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Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

et al. 2017

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The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber-Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites.

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Section: Neurosteroid E2 Is Necessary For Vor Adaptationsupporting

confidence: 77%

“…Consistent with these findings, it has been shown that acute inhibition of E2 synthesis also exerts rapid effects on spatial learning, working memory and fear extinction (Alejandre-Gomez et al 2007;Graham and Milad 2014;Moradpour et al 2006). …”

Section: Introductionsupporting

confidence: 55%

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

et al. 2017

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“…This is consistent with other research demonstrating rapid effects of aromatase inhibition on male behavior. For example, acute inhibition of aromatase modulates working memory in rats (Alejandre-Gomez et al 2007), the withdrawal response from a painful stimulus in quail (Evrard and Balthazart 2004), and sexual behavior in mice (Taziaux et al 2007). Also consistent are reports that aromatase activity itself is rapidly modulated by glutamate agonists that impact intracellular calcium concentrations (Balthazart et al 2006), and aromatase activity is also modulated by phosphorylation processes (Charlier et al 2011).…”

mentioning

confidence: 79%

“…Doses in this range have previously been shown to have rapid effects on behavior (Alejandre-Gomez et al 2007;Taziaux et al 2007). A fourth group of rats received an equivalent volume of vehicle at one of these time points, and were subsequently collapsed into one group (group Vehicle).…”

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confidence: 99%

Inhibition of estradiol synthesis impairs fear extinction in male rats

Graham

Milad

2014

Learn. Mem.

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Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole, significantly impairs extinction recall in male rats. This deficit in extinction recall is not due to state-dependent memory formation and is completely abolished by coadministration of estradiol. Our data suggest that estradiol may be just as important in the regulation of fear extinction in males as it is in females.Fear extinction is a laboratory model of exposure therapy for anxiety disorders (Graham and Milad 2011;Milad and Quirk 2012;Parsons and Ressler 2013). During extinction training a feared conditioned stimulus (CS) is repeatedly presented in the absence of the aversive unconditioned stimulus (US), until fear responses decline. Long-term retention of extinction is tested the following day by presenting the extinguished CS and measuring fear responses. Although the vast majority of research on fear extinction has been conducted using male rodents, more recent research has focused on fear extinction in females. The key finding that has emerged is that fear extinction is subject to considerable control by sex hormones, particularly estradiol (Lebron-Milad and Milad 2012). For example, fluctuations in estradiol across the menstrual cycle are correlated with the success of extinction; women and female rats that undergo extinction learning during the low estradiol phase exhibit impaired extinction recall the following day, relative to those undergoing extinction learning during the high estradiol phase (Chang et al. 2009;Milad et al. 2009Milad et al. , 2010Zeidan et al. 2011;Glover et al. 2012;Graham and Milad 2013;Rey et al. 2013). A single dose of estradiol prior to extinction training abolishes these extinction deficits in healthy women (Graham and Milad 2013). Furthermore, in female rodents, estrogen agonists enhance, whereas estrogen antagonists impair, extinction consolidation (Chang et al. 2009;Milad et al. 2009). Finally, hormonal contraceptives, which inhibit estradiol synthesis, impair extinction in both rats and women (Graham and Milad 2013). Hormone-associated disruptions in extinction have been suggested as a potential mechanism contributing to women's increased vulnerability to anxiety disorders Graham and Milad 2013). Indeed, low estradiol levels have been associated with diminished extinction learning and increased symptom severity in women with posttraumatic stress disorder (Glover et al. 2012).Is the influence of estradiol on fear extinction unique to females, or could estradiol also regulate fear extinction in males? Studies that have demonstrated that, in both rats and humans, females exhibit similar extinction recall to males when they are extinguished during the high estradiol phase of the menstrual cycle, and exhibit impaired extinction recal...

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“…Used to prevent osteoporosis, it has been shown that after three years of treatment raloxifene did not affect overall cognitive scores [43]. The Multiple Outcomes of Raloxifene Evaluation (MORE) study of 7478 women, reported finding that raloxifene treatment lowered the risk of cognitive decline in word list recall test and there was no overall effect on cognitive function (Table 1) [44]. A subset of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Study of Tamoxifen and Raloxifene (STAR), the CoSTAR study for women at high risk for breast cancer did not find any cognitive effects of either drug (Table 1) [45].…”

Section: Raloxifenementioning

confidence: 99%

The Confounding Factor of Apolipoprotein E on Response to Chemotherapy and Hormone Regulation Altering Long-Term Cognition Outcomes

Acevedo¹

2012

Lipoproteins - Role in Health and Diseases

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Administration of an inhibitor of estrogen biosynthesis facilitates working memory acquisition in male rats

Cited by 40 publications

References 52 publications

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

Inhibition of estradiol synthesis impairs fear extinction in male rats

The Confounding Factor of Apolipoprotein E on Response to Chemotherapy and Hormone Regulation Altering Long-Term Cognition Outcomes

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