Pentobarbital and ketamine suppress serum concentrations of sex hormones in the female rat

Lee, Chang Joo; Do, Byung-Rok; Kim, Jin Kyu; Yoon, Yong‐Dal

doi:10.1007/s005400070003

Cited by 12 publications

(11 citation statements)

References 17 publications

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“…However, in male Sprague-Dawley rats, ketamine treatment increased testosterone concentrations, but decreased LHRH (luteinizing hormone-releasing hormone) after 1 of administration and continued to significantly decrease after 24 h (Gould, 2008). In the present study, an effort to investigate whether ketamine influenced E2 concentration and CYP aromatase expression in zebrafish embryos was based on the reports that ketamine regulates a number of CYPs in mammals (Chen and Chen, 2010) and alters the serum concentrations of several hormones, such as progesterone, testosterone and E2 in cyclic rats (Lee et al, 2000). Estrogens are fundamental in the growth Figure 3.…”

Section: Discussionmentioning

confidence: 97%

“…The present study shows the ketamine concentration to be ~ 7.27 μM per embryo after exposure to 2 mM ketamine for 24 h. The data are comparable with 10 μM ketamine inducing neuronal damage in primary neurons from rat forebrain in culture (Liu et al ., ). Additionally, our current data demonstrate that 48 hpf embryos with such low internal ketamine concentrations had significantly lower levels of E2 compared with the control, an effect concordant with that in mammals in which a single dose of ketamine reduces E2 levels (Lee et al ., ).…”

Section: Discussionmentioning

confidence: 99%

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Ketamine attenuates cytochrome p450 aromatase gene expression and estradiol‐17β levels in zebrafish early life stages

Trickler

Guo

Cuevas

et al. 2013

J of Applied Toxicology

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Ketamine, a dissociative anesthetic, is a noncompetitive antagonist of N-methyl-D-aspartate-type glutamate receptors. In rodents and non-human primates as well as in zebrafish embryos, ketamine has been shown to be neurotoxic. In cyclic female rats, ketamine has been shown to decrease serum estradiol-17β(E2) levels. E2 plays critical roles in neurodevelopment and neuroprotection. Cytochrome p450 (CYP) aromatase catalyzes E2 synthesis from androgens. Although ketamine down-regulates a number of CYP enzymes in rodents, its effect on the CYP aromatase (CYP19) is not known. Zebrafish have been used as a model system for examining mechanisms underlying drug effects. Here, using wild-type (WT) zebrafish (Danio rerio) embryos, we demonstrate that ketamine significantly reduced E2 levels compared with the control. However, the testosterone level was elevated in ketamine-treated embryos. These results are concordant with data from mammalian studies. Ketamine also attenuated the expression of the ovary form of CYP aromatase (cyp19a1a) at the transcriptional level but not the brain form of aromatase, cyp19a1b. Exogenous E2 potently induced the expression of cyp19a1b and vtg 1, both validated biomarkers of estrogenicity and endocrine disruption, but not cyp19a1a expression. Attenuation of activated ERK/MAPK levels, reportedly responsible for reduced human cyp19 transcription, was also observed in ketamine-treated embryos. These results suggest that reduced E2 levels in ketaminetreated embryos may have resulted from the suppression of cyp19a1a transcription. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Ketamine attenuates cytochrome p450 aromatase gene expression and estradiol‐17β levels in zebrafish early life stages

Trickler

Guo

Cuevas

et al. 2013

J of Applied Toxicology

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“…Biological mechanisms underlying female-specific ketamine effects are largely unknown. Acute administration of ketamine has been reported to decrease serum sex hormones including estradiol, progesterone, and testosterone in female rats [ 41 ]. It is possible that repeated ketamine may have specific effects on women via sex hormones; however, the probable cause of the gender differences found in this study requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Gender differences in subjective discontinuation symptoms associated with ketamine use

Chen

Huang

Lin

2014

Subst Abuse Treat Prev Policy

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BackgroundRecent substance abuse research indicates gender differences in the substance-related epidemiology, biological responses, progression to dependence, medical consequences and treatments. Studies exploring human sex-different responses to ketamine are rare and there has been no systemic survey of gender differences in ketamine use. Determining whether females are more susceptible than males to ketamine withdrawal symptoms and adverse effects is important, because it associated with treatment retention and outcome in drug users.MethodsThe Taiwanese juridical system has implemented a new regulation on ketamine in the year 2009. Ketamine users who are caught by the police, are mandated to attend an educational program. We recruited ketamine offenders from February 2010 to May 2012 at the Kunming branch of the Taipei City Hospital, where the educational classes are held. A designed questionnaire was performed to gather information about demographic characteristics, discontinuation symptoms, concomitant use of other substances, and subjective experience of memory impairment or urinary discomforts, and to compare the gender differences.ResultsA total of 1,614 ketamine users were surveyed and most of them were males (83.8%), with an average age of 26.3 ± 5.4 years. Female ketamine users presented significantly more discontinuation symptoms such as anxiety, dysphoria, and tremors compared with male users. 72.4% of total ketamine users smoked cigarettes concomitantly. Male ketamine users had a higher rate of concomitant betel nut use, while female ketamine users had a higher rate of concomitant hypnotic and alcohol use. 76% of total ketamine users reported cognitive impairment and 51.6% mentioned urinary symptoms. Furthermore, female ketamine users self-reported significantly greater levels of severity in cognitive impairment and urinary discomforts compared with male users. Less than 10% of total ketamine users in our study reported the desire to transfer for medical intervention or treatment, despite the high rates of discontinuation symptoms and negative physical side effects.ConclusionsGender differences were noted in the subjective experience of discontinuation symptoms, concomitant substance use, and severity of impairment related to ketamine use. However, the probable cause of the gender differences found in this study requires further investigation. We hoped our study will stimulate further research in this field.

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“…A strong (> 70%) decline of endogenous steroid levels in the brain (progesterone, pregnenolone) occurs upon treatment of male rats with anaesthetic amounts of sodium pentobarbital (0.2 mmol/kg i.p., [ 29 ]). Plasma progesterone in female rats is also decreased after pentobarbital administration [ 32 ]. Thus, competition of endogenous steroids with 11 C-SA4503 binding in target organs was expected to be reduced after repeated treatment of Wistar rats with pentobarbital.…”

Section: Resultsmentioning

confidence: 99%

Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats

Rybczynska

Elsinga

Sijbesma

et al. 2009

Eur J Nucl Med Mol Imaging

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Purpose Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist 11 C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. Methods 11 C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. Results Binding of 11 C-SA4503 to C6 cells was increased (~50%) upon removal and decreased (~60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC 50 progesterone 33 nM).Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of 11 C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. Conclusions The binding of 11 C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids.

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Pentobarbital and ketamine suppress serum concentrations of sex hormones in the female rat

Abstract: Pentobarbital and ketamine decrease serum sex hormone concentrations in PMSG-primed female rats.

Cited by 12 publications

References 17 publications

Ketamine attenuates cytochrome p450 aromatase gene expression and estradiol‐17β levels in zebrafish early life stages

Ketamine attenuates cytochrome p450 aromatase gene expression and estradiol‐17β levels in zebrafish early life stages

Gender differences in subjective discontinuation symptoms associated with ketamine use

Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats

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