Impairment of maze learning in rats following long-term glucocorticoid treatments

Endo, Yutaka; Nishimura, Jun-ichi; Kimura, Fukuko

doi:10.1016/0304-3940(95)12296-6

Cited by 57 publications

(29 citation statements)

References 20 publications

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“…Given that dietary cholesterol does not cross the blood brain barrier in any appreciable amount (Bjorkhem & Meaney, 2004;Dietschy & Turley, 2001;Dietschy & Turley, 2004;Tuma & Hubbard, 2003), it remains to be determined how heart rate conditioning, which is controlled in part by the amygdala via the dorsal motor nucleus of the vagus, was increased as a result of a cholesterol-rich diet. The same would be true for the effects of cholesterol on rat water maze learning (Dufour et al, 2006) and previous research showing that addition of cholesterol to the diet of animals deficient in cholesterol or animals that have cholesterol synthesis blocked reverses learning and memory deficits (Endo, Nishimura, & Kimura, 1996;O'Brien et al, 2002;Voikar, Rauvala, & Ikonen, 2002;Xu et al, 1998).…”

Section: Discussionmentioning

confidence: 79%

Cholesterol enhances classical conditioning of the rabbit heart rate response

Schreurs

Smith-Bell

Darwish

et al. 2007

Behavioural Brain Research

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The cholesterol-fed rabbit is a model of atherosclerosis and has been proposed as an animal model of Alzheimer's disease. Feeding rabbits cholesterol has been shown to increase the number of beta amyloid immunoreactive neurons in the cortex. Addition of copper to the drinking water of cholesterol-fed rabbits can increase this number still further and may lead to plaque-like structures. Classical conditioning of the nictitating membrane response in cholesterol-fed rabbits is retarded in the presence of these plaque-like structures but may be facilitated in their absence. In a factorial design, rabbits fed 2% cholesterol or a normal diet (0% cholesterol) for 8 weeks with or without copper added to the drinking water were given trace classical conditioning using a tone and periorbital electrodermal stimulation to study the effects of cholesterol and copper on classical conditioning of heart rate and the nictitating membrane response. Cholesterol-fed rabbits showed significant facilitation of heart rate conditioning and conditioning-specific modification of heart rate relative to normal diet controls. Consistent with previous research, cholesterol had minimal effects on classical conditioning of the nictitating membrane response when periorbital electrodermal stimulation was used as the unconditioned stimulus. Immunohistochemical analysis showed a significant increase in the number of beta amyloid positive neurons in the cortex, hippocampus and amygdala of the cholesterol-fed rabbits. Supplementation of drinking water with copper increased the number of beta amyloid positive neurons in the cortex of cholesterol-fed rabbits but did not produce plaque-like structures or have a significant effect on heart rate conditioning. The data provide additional support for our finding that, in the absence of plaques, dietary cholesterol may facilitate learning and memory. Cholesterol enhances rabbit heart rate conditioningThe cholesterol-fed rabbit has been used as an animal model of atherosclerosis since 1913 when Anitchkow first demonstrated that a cholesterol diet induced vascular lesions (Bocan, 1998;Fan & Watanabe, 2000;Finking & Hanke, 1997;Moghadasian, 2002). More recently, the cholesterol-fed rabbit has been proposed as an animal model of Alzheimer's disease (Ghribi, Larsen, Schrag, & Herman, 2006;Sjogren, Mielke, Gustafson, Zandi, & Skoog, 2006 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Sparks, 1997;Sparks, Martin, Gross, & Hunsaker III, 2000;Zatta, Zambenedetti, Stella, & Licastro, 2002). Based on the observation that patients with heart disease had beta amyloid st...

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Section: Discussionmentioning

confidence: 79%

Cholesterol enhances classical conditioning of the rabbit heart rate response

Schreurs

Smith-Bell

Darwish

et al. 2007

Behavioural Brain Research

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“…Studies that have found spatial learning and memory deficits after chronic glucocorticoid exposure differ from the present research. These studies used a protocol that may have produced neuron loss, and/or glucocorticoid treatment continued during training and testing, which combines the chronic and acute actions of glucocorticoids on performance (Bardgett et al, 1994(Bardgett et al, , 1996Dachir et al, 1995;Endo et al, 1996;McLay et al, 1998;Ramos-Remus et al, 2002). Indeed, CoburnLitvak et al (2003) found spatial memory deficits when chronic glucocorticoid treatment extended to 56 d. These findings support the interpretation that CA3 dendritic retraction is not responsible for spatial learning and memory deficits (Conrad, 2006).…”

Section: Discussionmentioning

confidence: 86%

Chronic Glucocorticoids Increase Hippocampal Vulnerability to Neurotoxicity under Conditions That Produce CA3 Dendritic Retraction But Fail to Impair Spatial Recognition Memory

Conrad¹,

McLaughlin²,

Harman³

et al. 2007

J. Neurosci.

129

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We previously found that chronic stress conditions producing CA3 dendritic retraction and spatial memory deficits make the hippocampus vulnerable to the neurotoxin ibotenic acid (IBO). The purpose of this study was to determine whether exposure to chronic corticosterone (CORT) under conditions that produce CA3 dendritic retraction would enhance CA3 susceptibility to IBO. Male Sprague Dawley rats were chronically treated for 21 d with CORT in drinking water (400 g/ml), and half were given daily injections of phenytoin (40 mg/kg), an antiepileptic drug that prevents CA3 dendritic retraction. Three days after treatments stopped, IBO was infused into the CA3 region. Conditions producing CA3 dendritic retraction (CORT and vehicle) exacerbated IBO-induced CA3 damage compared with conditions in which CA3 dendritic retraction was not observed (vehicle and vehicle, vehicle and phenytoin, CORT and phenytoin). Additionally, spatial recognition memory was assessed using the Y-maze, revealing that conditions producing CA3 dendritic retraction failed to impair spatial recognition memory. Furthermore, CORT levels in response to a potentially mild stressor (injection and Y-maze exposure) stayed at basal levels and failed to differ among key groups (vehicle and vehicle, CORT and vehicle, CORT and phenytoin), supporting the interpretations that CORT levels were unlikely to have been elevated during IBO infusion and that the neuroprotective actions of phenytoin were not through CORT alterations. These data are the first to show that conditions with prolonged glucocorticoid elevations leading to structural changes in hippocampal dendritic arbors can make the hippocampus vulnerable to neurotoxic challenges. These findings have significance for many disorders with elevated glucocorticoids that include depression, schizophrenia, Alzheimer's disease, and Cushing's disease.

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“…The normal performance from chronically stressed rats treated with tianeptine and impaired performance from chronically stressed rats given vehicle strongly suggested that hippocampal atrophy was responsible for the spatial memory deficit. Spatial learning and memory were also impaired after exposure to stress levels of corticosterone for weeks or months (Luine et al, 1993;Dachir et al, 1993;Arbel et al, 1994;Bardgett et al, 1994;Bodnoff et al, 1995;Endo et al, 1996;Krugers et al, 1997, but cf. Bardgett et al, 1996Clark et al, 1995).…”

Section: Introductionmentioning

confidence: 96%

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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Impairment of maze learning in rats following long-term glucocorticoid treatments

Cited by 57 publications

References 20 publications

Cholesterol enhances classical conditioning of the rabbit heart rate response

Cholesterol enhances classical conditioning of the rabbit heart rate response

Chronic Glucocorticoids Increase Hippocampal Vulnerability to Neurotoxicity under Conditions That Produce CA3 Dendritic Retraction But Fail to Impair Spatial Recognition Memory

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

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