Effect of the glucocorticoid receptor antagonist RU486 on MK-801 induced behavioural sensitisation

Lefevre, Emilia M.; Medley, Gregory; Reeks, Timothy; Schmeißer, Alexander; Eyles, Darryl W.

doi:10.1371/journal.pone.0176156

Cited by 7 publications

(3 citation statements)

References 47 publications

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“…CORT levels were quantified by an in-house LC–MS/MS protocol used previously in the group 26 . Plasma was dispensed in 1:1 acetone:ethanol, and 200μL of deuterated corticosterone –[ 2 H 4 ] was added as an internal standard.…”

Section: Methodsmentioning

confidence: 99%

Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome

Petty

Cui

Ali

et al. 2021

Sci Rep

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An increase in dopamine (DA) synthesis capacity in the dorsal striatum (DS) during the prodromal stage of schizophrenia becomes more pronounced as patients progress to the full disorder. Understanding this progression is critical to intervening in disease course. We developed an animal model—Enhanced Dopamine in Prodromal Schizophrenia (EDiPS)—which uses a genetic construct to increase DA synthesis capacity in the DS of male rats. We assessed pre-pulse inhibition (PPI) and amphetamine (AMPH)-induced locomotion (0.6 mg/kg) in EDiPS animals longitudinally after post-natal day 35 (when the EDiPS construct is administered). We also assessed their response to repeated acute restraint stress. In adult EDiPS animals, we measured baseline and evoked extracellular DA levels, and their stereotyped responses to 5 mg/kg AMPH. AMPH-induced hyperlocomotion was apparent in EDiPS animals 6-weeks after construct administration. There was an overall PPI deficit in EDiPS animals across all timepoints, however the stress response of EDiPS animals was unaltered. Adult EDiPS animals show normal baseline and potassium-evoked DA release in the DS. These findings suggest that key behavioural phenotypes in EDiPS animals show a progressive onset, similar to that demonstrated by patients as they transition to schizophrenia. The EDiPS model could therefore be used to investigate the molecular mechanisms underlying the prodrome of schizophrenia.

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Section: Methodsmentioning

confidence: 99%

Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome

Petty

Cui

Ali

et al. 2021

Sci Rep

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“…Because the stress of FST may influence the behavior in the EPM, we did not counterbalance the two tests. Future studies should evaluate the individual contribution of the estrogen and progesterone receptors; it must be noted that mifepristone can also bind to glucocorticoid receptors and modify emotional behaviors (Lefevre et al., 2017). The depression‐like behavior observed in female rats occurred with a delayed onset, which is consistent with the delayed nature of mild TBI‐induced depression in humans.…”

Section: Discussionmentioning

confidence: 99%

Sex and estrous‐phase dependent alterations in depression‐like behavior following mild traumatic brain injury in adolescent rats

Giacometti

Huh

Raghupathi

2021

J of Neuroscience Research

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Following mild traumatic brain injury (TBI), high school and collegiate‐aged females tend to report more emotional symptoms than males. Adolescent male and female rats (35 days old) were subjected to mild TBI and evaluated for anxiety‐ and depression‐like behaviors using the elevated plus maze and forced swim test (FST), respectively, and cellular alterations. Injured brains did not exhibit an overt lesion, atrophy of tissue or astrocytic reactivity underneath the impact site at 6‐week post‐injury, suggestive of the mild nature of trauma. Neither male nor female brain‐injured rats exhibited anxiety‐like behavior at 2 or 6 weeks, regardless of estrous phase at the time of behavior testing. Brain‐injured male rats did not exhibit any alterations in immobility, swimming and climbing times in the FST compared to sham‐injured rats at either 2‐ or 6‐week post‐injury. Brain‐injured female rats did, however, exhibit an increase in immobility (in the absence of changes in swimming and climbing times) in the FST at 6 weeks post‐injury only during the estrus phase of the estrous cycle, suggestive of a depression‐like phenotype. Combined administration of the estrogen receptor antagonist, tamoxifen, and the progesterone receptor antagonist, mifepristone, during proestrus was able to prevent the depression‐like phenotype observed during estrus. Taken together, these data suggest that female rats may be more vulnerable to exhibiting behavioral deficits following mild TBI and that estrous phase may play a role in depression‐like behavior.

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“…mifepristone; Cayman Chemical) dissolved in 30% Kolliphor, 1% DMSO and Tween 20 (3 drops) to a dose of 20 mg/kg (i.p.) administered once daily for 8 days [ 42 , 53 , 54 ].…”

Section: Methodsmentioning

confidence: 99%

HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice

Salahuddin

Mahdi

Sulochana

et al. 2021

Viruses

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Human immunodeficiency virus (HIV) is associated with neuroendocrine dysfunction which may contribute to co-morbid stress-sensitive disorders. The hypothalamic-pituitary-adrenal (HPA) or -gonadal (HPG) axes are perturbed in up to 50% of HIV patients. The mechanisms are not known, but we have found the HIV-1 trans-activator of transcription (Tat) protein to recapitulate the clinical phenotype in male mice. We hypothesized that HPA and/or HPG dysregulation contributes to Tat-mediated interactions with oxycodone, an opioid often prescribed to HIV patients, in females. Female mice that conditionally-expressed the Tat1–86 protein [Tat(+) mice] or their counterparts that did not [Tat(−) control mice] were exposed to forced swim stress (or not) and behaviorally-assessed for motor and anxiety-like behavior. Some mice had glucocorticoid receptors (GR) or corticotropin-releasing factor receptors (CRF-R) pharmacologically inhibited. Some mice were ovariectomized (OVX). As seen previously in males, Tat elevated basal corticosterone levels and potentiated oxycodone’s psychomotor activity in females. Unlike males, females did not demonstrate adrenal insufficiency and oxycodone potentiation was not regulated by GRs or CRF-Rs. Rather OVX attenuated Tat/oxycodone interactions. Either Tat or oxycodone increased anxiety-like behavior and their combination increased hypothalamic allopregnanolone. OVX increased basal hypothalamic allopregnanolone and obviated Tat or oxycodone-mediated fluctuations. Together, these data provide further evidence for Tat-mediated dysregulation of the HPA axis and reveal the importance of HPG axis regulation in females. HPA/HPG disruption may contribute vulnerability to affective and substance use disorders.

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Effect of the glucocorticoid receptor antagonist RU486 on MK-801 induced behavioural sensitisation

Cited by 7 publications

References 47 publications

Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome

Positive symptom phenotypes appear progressively in “EDiPS”, a new animal model of the schizophrenia prodrome

Sex and estrous‐phase dependent alterations in depression‐like behavior following mild traumatic brain injury in adolescent rats

HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice

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