Glucocorticoid treatment increases the ability of CRH to induce seizures

doi:10.1016/0304-3940(94)90132-5

Neuroscience Letters

Volume 174, Issue 1, 6 June 1994, Pages 113-116

https://doi.org/10.1016/0304-3940(94)90132-5 Get rights and content

Abstract

We examined whether glucocorticoids could enhance the ability of corticotropin-releasing hormone (CRH) to induce seizures. Rats were treated with systemic glucocorticoids (dexamethasone, 100 μg) or vehicle for either 3 days (chronic) or 2 h (acute) before intracerebroventricular CRH (3 or 10 μg) or saline injections and then monitored for 8 h following each injection. Our results suggest that chronic, but not acute, glucocorticoid pretreatment increases the likelihood of CRH-induced seizures.

References (15)

M.F. Dallman et al.
Regulation of ACTH secretion: variations on a theme of B
Recent Prog. Horm. Res.
(1987)
C.L. Ehlers et al.
Corticotropin releasing factor produces increases in brain excitability and convulsive seizures in rats
Brain Res.
(1983)
M.A. Kling et al.
Facilitation of cocaine-kindling by glucocorticoids in rats
Brain Res.
(1993)
D.C. McIntyre et al.
Adrenalectomy: protection from kindled convulsion induced dissociation in rats
Physiol. Behav.
(1978)
G. Weiss et al.
The effect of adrenalectomy on the circadian variation in the rate of kindled seizure development
Brain Res.
(1993)
G.K. Weiss et al.
Amygdala kindling rate is altered in rats with a deficit in the responsiveness of the hypothalamo-pituitary-adrenal axis
Neurosci. Lett.
(1993)
S.R.B. Weiss et al.
CRF-induced seizures and behavior: interactions with amygdala kindling
Brain Res.
(1986)

There are more references available in the full text version of this article.

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Interactive effects of prenatal exposure to restraint stress and alcohol on pentylenetetrazol-induced seizure behaviors in rat offspring
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With respect to epileptic behaviors, in the present study, the COS blood levels and the number, duration, and occurrence of the focal and tonic-clonic seizures significantly increased in pups of the RS group compared to the control pups, which in general indicates potentiation of seizure behaviors in the stressed pups. These results are consistent with those of previous studies that showed the effect of stress on seizure susceptibility to be at least in part due to involvement, activities, and engagement of the HPA system (Edwards et al., 2002; Maguire & Salpekar, 2013; Reddy & Rogawski, 2002; Rosen et al., 1994; Sadaghiani & Saboory, 2010; Yang, Zou, Wang, & Ding, 2011). The significantly elevated COS levels in pups of the RS group on P6 and P15 clearly indicate that they were exposed to stress during gestation.
Prenatal exposure to stress or alcohol increases vulnerability of brain regions involved in neurobehavioral development and programs susceptibility to seizure. To examine how prenatal alcohol interferes with stress-sensitive seizures, corticosterone (COS) blood levels and pentylenetetrazol (PTZ)-induced seizure behaviors were investigated in rat pups, prenatally exposed to stress, alcohol, or both. Pregnant rats were exposed to stress and saline/alcohol on 17, 18, and 19 days of pregnancy and divided into four groups of control–saline (CS), control–alcohol (CA), restraint stress–saline (RS), and restraint stress–alcohol (RA). In CS/CA groups, rats received saline/alcohol (20%, 2 g/kg, intraperitoneally [i.p.]). In RS/RA groups, rats were exposed to restraint stress by being held immobile in a Plexiglas^® tube (twice/day, 1 h/session), and received saline/alcohol, simultaneously. After parturition, on postnatal days 6 and 15 (P6 & P15), blood samples were collected from the pups to determine COS level. On P15 and P25, PTZ (45 mg/kg) was injected into the rest of the pups and seizure behaviors were then recorded. COS levels increased in pups of the RS group but not in pups of the RA group. Both focal and tonic-clonic seizures were prevalent and severe in pups of the RS group, whereas only focal seizures were prominent in pups of the CA group. However, pups prenatally exposed to co-administration of alcohol and stress, unexpectedly, did not show additive epileptic effects. The failure of pups prenatally exposed to alcohol to show progressive or facilitatory epileptic responses to stressors, indicates decreased plasticity and adaptability, which may negatively affect HPA-axis performance or hippocampal structure/function.
Evolutionary conservation of glucocorticoids and corticotropin releasing hormone: Behavioral and physiological adaptations
2011, Brain Research
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In many species (primates, rodents, reptiles, and amphibians), CRH is expressed in the amygdala, bed nucleus of the stria terminalis (BNST), and medial pallium, and its expression, and that of the immediate early gene c-fos, are increased following exposure to a stressor as well as the level of corticosterone being elevated (Yao et al., 2008a, 2008b; Denver and Crespi, 2006). CRH and corticosterone are well known across phyla to promote locomotor activity and impact diverse forms of behaviors (Moore and Rose, 2002; Rosen et al., 1994; Wingfield, 2004) including sexual, feeding and fear related behaviors among others. In the frog, just like mammals, CRH is increased by treatment with corticosterone (given in their bathing water over several days).
Glucocorticoids and corticotropin releasing hormone (CRH) underlie the physiology of change and adaptation. Both the steroid and peptide are quite ancient. The genes that underlie the production of these information molecules stretch back millions of years. The regulatory mechanisms of glucocorticoids have both restraining and enhancing capabilities on CRH gene expression. While restraint of CRH by glucocorticoids is a fundamental physiological feature of limiting CRH expression from over-use and exhaustion, CRH is also enhanced by glucocorticoids at both the level of extra-hypothalamic CRH sites and at the level of the placenta and fetal programming in the brain. This latter function of glucocorticoids increasing CRH gene expression underlies the physiology of change that underlies diverse adaptive functions.
Scopolamine-induced convulsions in fasted mice after food intake: Evaluation of the sedative effect in the suppression of convulsions
2010, Epilepsy Research
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It has been shown that after fasting for 12, 24 and 48 h, the stress hormone corticosterone level rises in mice (Luque et al., 2007) and CRH (corticotropin-releasing hormone) release increases in rats deprived of food for 48 h (Maeda et al., 1994). Since animals develop convulsions after CRH administration (Rosen et al., 1994) or exposure to stress (Rhodes et al., 2004), we used different attempts during deprivation period to counter food deprivation-induced neuroendocrine responses for the prevention of seizures in fasted animals. However, neither dexamethasone use to suppress pituitary–adrenocortical activity (Gomez et al., 1998), nor clonidine and diazepam use to ameliorate stress during deprivation could provide effective treatments in convulsions in 48-h (Enginar and Nurten, 2005) and 24-h (unpublished data of a thesis study) fasted animals, respectively.
Food intake triggers convulsions in fasted mice and rats treated with antimuscarinic drugs, scopolamine or atropine. Most of the drugs produced anticonvulsant efficacy in these convulsions have sedative effects. Thus, the present study was performed to evaluate the contribution of sedation in the suppression of convulsions by using sedative drugs chlorpromazine, morphine, amitriptyline and diphenhydramine. Mice fasted for 24 h and treated with 3 mg/kg scopolamine developed convulsions soon after refeeding. Treatment of chlorpromazine and morphine during food deprivation did not provide a preventive effect in the development of convulsions observed after food intake in fasted animals. Pretreatment of amitriptyline, but not diphenhydramine, before scopolamine treatment suppressed the incidence of convulsions. Present results could not clearly demonstrate the role played by sedative effect in suppression of convulsions in fasted animals.
From Malthus to motive: How the HPA axis engineers the phenotype, yoking needs to wants
2006, Progress in Neurobiology
The hypothalamo–pituitary–adrenal (HPA) axis is the critical mediator of the vertebrate stress response system, responding to environmental stressors by maintaining internal homeostasis and coupling the needs of the body to the wants of the mind. The HPA axis has numerous complex drivers and highly flexible operating characterisitics. Major drivers include two circadian drivers, two extra-hypothalamic networks controlling top-down (psychogenic) and bottom-up (systemic) threats, and two intra-hypothalamic networks coordinating behavioral, autonomic, and neuroendocrine outflows. These various networks jointly and flexibly control HPA axis output of periodic (oscillatory) functions and a range of adventitious systemic or psychological threats, including predictable daily cycles of energy flow, actual metabolic deficits over many time scales, predicted metabolic deficits, and the state-dependent management of post-prandial responses to feeding. Evidence is provided that reparation of metabolic derangement by either food or glucocorticoids results in a metabolic signal that inhibits HPA activity. In short, the HPA axis is intimately involved in managing and remodeling peripheral energy fluxes, which appear to provide an unidentified metabolic inhibitory feedback signal to the HPA axis via glucocorticoids. In a complementary and perhaps a less appreciated role, adrenocortical hormones also act on brain to provide not only feedback, but feedforward control over the HPA axis itself and its various drivers, as well as coordinating behavioral and autonomic outflows, and mounting central incentive and memorial networks that are adaptive in both appetitive and aversive motivational modes. By centrally remodeling the phenotype, the HPA axis provides ballistic and predictive control over motor outflows relevant to the type of stressor. Evidence is examined concerning the global hypothesis that the HPA axis comprehensively induces integrative phenotypic plasticity, thus remodeling the body and its governor, the brain, to yoke the needs of the body to the wants of the mind. Adverse side effects of this yoking under conditions of glucocorticoid excess are discussed.
A neuroendocrine mechanism for sustaining fear
2005, Trends in Neurosciences
Fear is an adaptive response to recognition of a potentially dangerous event. Glucocorticoids are essential for maintaining a wide variety of behavioral events by their regulation of numerous genes; one such gene encodes corticotrophin-releasing hormone (CRH). CRH is involved in diverse behavioral responses to changing environmental demands. In this review, we focus on one aspect of glucocorticoid regulation of CRH – namely, fear-related responses to diverse classes of adverse events, such as those represented by contextual and cue-specific stimuli. Three extra-hypothalamic forebrain sites appear crucial for fear-related behavioral responses: the amygdala and the bed nucleus of the stria terminalis for sustaining adaptive fear-related behaviors, and the medial prefrontal cortex for modulating fear-related behaviors. Central regulation of CRH by glucocorticoids is important for adaptive and sustained fear-related behaviors, and its aberration is associated with anxiety and depressive disorders.
Stress induces CRF release in the paraventricular nucleus, and both CRF and GABA release in the amygdala
2004, Physiology and Behavior
In the hypothalamus, corticotropin-releasing factor (CRF) initiates the hypothalamic–pituitary–adrenal (HPA) axis response to stress, resulting in the release of glucocorticoids, including cortisol. Extrahypothalamic CRF, particularly in the limbic system, also appears to play a role in the stress response. To further define brain CRF response to stress, immunosensor-based microdialysis probes were used to measure the extracellular levels of CRF in the paraventricular nucleus of the hypothalamus (PVN) and in the amygdala of sheep during a predator (dog) exposure stress. In addition, gamma amino butyric acid (GABA) was measured in the amygdala and cortisol was measured in venous blood. Exposure to the predator stress increased CRF in the PVN and both CRF and GABA in the amygdala. These were followed in time by a rise in venous cortisol. Application of a CRF antagonist to the amygdala, immediately prior to stress, had a small effect on the subsequent observed stress responses. This treatment, however, significantly reduced the responses to a repeat stress administered 2 days later, compared to nontreated animals. Application of a GABA antagonist to the amygdala prior to stress had no effect on the subsequent observed stress response but increased the response to the stress repeated 2 days later. Perfusion with 4-aminopyridine, a neuronal depolarising agent, into the PVN induced a release of CRF accompanied shortly thereafter by a small increase in CRF in the amygdala, and 5–10 min later by an increase in venous cortisol. Perfusion into the amygdala increased the levels of both CRF and GABA but had no effect on either PVN CRF or venous cortisol. These data support roles for both the PVN and amygdala in stress responsiveness. It suggests further that actions at the amygdala can strongly influence subsequent responsiveness to a further stress, mediated in part by both CRF and GABA actions.

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Glucocorticoid treatment increases the ability of CRH to induce seizures

Abstract

Recent Prog. Horm. Res.

Brain Res.

Brain Res.

Physiol. Behav.

Brain Res.

Neurosci. Lett.

Brain Res.