Effect of 2-methyl-1,2-bis-/3-pyridyl/-1-propanone (SU-4885) on adrenocortical secretion in normal and hypophysectomized rats

Strashimirov, D; Bohus, B.

doi:10.1016/0039-128x(66)90024-9

Cited by 19 publications

(14 citation statements)

References 10 publications

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“…The 200 mg/kg dose of metyrapone chosen was based upon prior studies that used similar levels to investigate corticosterone actions on brain damage (Strashimirov and Bohus, 1966;Stein and Sapolsky, 1988;Smith-Swintosky et al, 1996;Krugers et al, 1998). However, recent reports indicate that a lower dose was successfully used to prevent corticosterone surges during stress while behaviour was measured (Roozendaal et al, 1996a;Loscertales et al, 1997;de Quervain et al, 1998;Liu et al, 1999).…”

Section: Control Studiesmentioning

confidence: 99%

“…Metyrapone is a synthetic steroidogenesis inhibitor that blocks 11 β-hydroxylase, the enzyme responsible for converting deoxycorticosterone to corticosterone within the adrenal cortex (Schimmer and Parker, 1996). The result is attenuation of corticosterone synthesis and release in stressed animals (Strashimirov and Bohus, 1966) without disruption of basal corticosterone levels or adrenal medullary hormone release (Roozendaal et al, 1996a). The one-time use of metyrapone allows the long-term effects of prior chronic stress on hippocampal-dependent memory to be observed without interference from the temporary surge of corticosterone during fear conditioning training.…”

Section: Introductionmentioning

confidence: 99%

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Metyrapone Reveals That Previous Chronic Stress Differentially Impairs Hippocampal-dependent Memory

Conrad

Mauldin-Jourdain

Hobbs

2001

Stress

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Chronic stress facilitates fear conditioning in rats with hippocampal neuronal atrophy and in rats in which the atrophy is prevented with tianeptine, a serotonin re-uptake enhancer. The purpose of this study was to determine whether the lack of dissociation between fear conditioning performance and hippocampal integrity was masked by the presence of endogenous corticosteroids during training. As in previous studies, rats were stressed by daily restraint (6 h/day for 21 days), trained in the conditioning chamber (day 23), and then assessed for conditioned fear (day 25) at a time when hippocampal dendritic atrophy persists. On the training day, half of the control and stressed rats were injected with metyrapone to reduce corticosterone release. Two hours later, two paired or unpaired presentations of tone and footshock were delivered. Although metyrapone reduced conditioned fear in all rats, only stressed rats showed dissociated fear conditioning (i.e. tone conditioning was reduced while contextual conditioning was eliminated). Chronically stressed rats, regardless of metyrapone treatment displayed more rearing in the open field when tested immediately after the completion of fear conditioning. These data support the hypothesis that increased emotionality and enhanced fear conditioning exhibited by chronically stressed rats may be due to endogenous corticosterone secretion at the time of fear conditioned training. Moreover, these data suggest that chronic stress impairs hippocampal-dependent processes more robustly than hippocampal-independent processes after metyrapone to reduce corticosterone secretion during aversive training.

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Section: Control Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metyrapone Reveals That Previous Chronic Stress Differentially Impairs Hippocampal-dependent Memory

Conrad

Mauldin-Jourdain

Hobbs

2001

Stress

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“…tetrahydroxydeoxycorticosterone; Strashmirov & Bohus, 1966). Furthermore, metyrapone blocks synthesis of serotonin in the rat hippocampus (Korte-Bouws et 37 a!., 1996).…”

Section: Metyraponementioning

confidence: 99%

Glucocorticoids are required for extinction of predator stress-induced hyperarousal

Clay

Hebert

Gill

et al. 2011

Neurobiology of Learning and Memory

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Extinction of fearful behavior induced by severe stress was studied using predator stress. Predator stress involves a ten minute unprotected exposure of a rodent to a cat which induces long-lasting changes in anxiety-like behaviours and hyperarousal (increased acoustic startle response) (Adamec & Shallow, 1993; Adamec et al., 200 I;Cohen et al., 2004). In the present set of experiments, three questions were addressed using predator stressed mice. First, can predator stress-induced fear memories be extinguished? Second, is the extinction of predator stress-induced fear memories glucocorticoid-dependent? Finally, is re-exposure to the predator stress context necessary to see glucocorticoid's effects on predator stress-induced fear memories?Extinction was induced by re-exposing mice to the predator stress room in the absence of the cat. This repeated re-exposure to predator stress context increased activity in the predator stress context implying extinction of predator stress-induced immobility, a context-dependent fear memory. Repeated re-exposures to the predator stress context also decreased subsequent hyperarousal (acoustic startle response) and generalized anxiety-like behaviour. These fearful behaviors were predator stress context independent, having been tested in environments different from the cat exposure room. Furthermore, blocking glucocorticoid synthesis with metyrapone during repeated exposures to the predator stress context had no effect on activity. Therefore, reducing corticosterone levels did not affect extinction of the predator stress-induced, context-dependent fear memory.However, metyrapone given during repeated exposures to the predator stress context prevented extinction of predator stress-induced hyperarousal. These results suggest that extinction of predator stress-induced, context-independent fear memory is dependent on Ill the presence of endogenous corticosterone during the extinction trial . Finally, reexposure to the predator stress context was found to be necessary to see glucocorticoid's effects on predator stress-induced fear memories. This was determined by repeated injection of metyrapone over days without re-exposure to the predator stre s context.

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Section: Introductionmentioning

confidence: 99%

“…The enhancing effects of systemic injections of amphetamine, 4-OH amphetamine, and epinephrine on memory for inhibitory avoidance training were examined in rats pretreated with a vehicle solution or metyrapone, a drug that inhibits 1 1 3-hydroxylase, a rate-limiting enzyme in corticosterone synthesis (29,30 second experiment was conducted to exclude the possibility that the effects found on retention performance were due to sensory or motivational influences on acquisition. In this second experiment, rats were pretreated with metyrapone and received injections of the adrenergic agents immediately after training.…”

mentioning

confidence: 99%

Adrenocortical suppression blocks the memory-enhancing effects of amphetamine and epinephrine.

Roozendaal

Carmi

McGaugh

1996

Proc. Natl. Acad. Sci. U.S.A.

113

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This study examined glucocorticoidadrenergic interactions in modulating acquisition and memory storage for inhibitory avoidance training. Systemically (s.c.) administered amphetamine (1 mg/kg), but not epinephrine (0.1 mg/kg) or the peripherally acting amphetamine derivative 4-OH amphetamine (2 mg/kg), given to rats shortly before training facilitated acquisition performance in a continuous multiple-trial inhibitory avoidance (CMIA) It is well established that adrenal hormones are released during training in emotionally motivated tasks (1-3) and influence neurobiological mechanisms underlying regulation of memory storage (4-6). Systemic injections of the adrenomedullary hormone epinephrine produce dose-dependent enhancement of retention performance when given to rats and mice shortly after training in aversive and appetitive learning tasks (7-10).Earlier evidence suggesting that peripheral catecholamines modulate memory storage came from experiments examining the effects of systemic injections of amphetamine. In rats and mice, amphetamine produces dose-and time-dependent enhancement of memory storage (11)(12)(13)(14)(15)(16)(17). The effects of posttraining injections of amphetamine on memory are attenuated by surgical removal of the adrenal medulla (13), the primary source of circulating epinephrine (18). This finding suggests that the effects of amphetamine on memory storage are due, at least in part, to an influence on the release of catecholamines from peripheral storage sites (19). This view is supported by evidence that 4-OH amphetamine, a derivative of amphetamine with a limited capacity to enter the brain (20),The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. also facilitates retention when given immediately after training (12,14,17).Training in aversively motivated learning tasks is also known to stimulate the adrenocortical system, resulting in increased plasma levels of corticosterone (3, 21). There is extensive evidence that glucocorticoids modulate memory consolidation (22)(23)(24)(25)(26). Furthermore, findings of experiments using adrenalectomized (ADX) rats indicate that the level of circulating corticosterone is a major factor in determining the sensitivity of epinephrine in modulating memory storage (27,28), suggesting an interaction between sympathoadrenal and adrenocortical systems in the modulation of memory storage for emotionally influenced tasks.The present experiments examined glucocorticoidadrenergic interactions in the regulation of memory storage in adrenally intact rats. The enhancing effects of systemic injections of amphetamine, 4-OH amphetamine, and epinephrine on memory for inhibitory avoidance training were examined in rats pretreated with a vehicle solution or metyrapone, a drug that inhibits 1 1 3-hydroxylase, a rate-limiting enzyme in corticosterone synthesis (29,30 Apparatus and Procedures. Two variants of ...

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Effect of 2-methyl-1,2-bis-/3-pyridyl/-1-propanone (SU-4885) on adrenocortical secretion in normal and hypophysectomized rats

Cited by 19 publications

References 10 publications

Metyrapone Reveals That Previous Chronic Stress Differentially Impairs Hippocampal-dependent Memory

Metyrapone Reveals That Previous Chronic Stress Differentially Impairs Hippocampal-dependent Memory

Glucocorticoids are required for extinction of predator stress-induced hyperarousal

Adrenocortical suppression blocks the memory-enhancing effects of amphetamine and epinephrine.

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