Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats.
Exposure to early stressful adverse life events may increase vulnerability to psychopathology in adult life. There are important memory disturbances in stress-related psychiatric disorders. Therefore, there is much interest in understanding the mechanisms responsible for interactions between stress and cognition. Male Wistar rats that experienced 3-h daily separations from the dam during the first 3 weeks of life (maternal separation, MS) showed in adulthood a depressive-like behaviour in the forced swimming test, increased hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and elevated CRF mRNA in the paraventricular nucleus of the hypothalamus (PVN). In the hippocampus of MS rats, there was a lower glucocorticoid receptor density. MS produced significant learning impairments both in the Morris water maze and in the novel object recognition test (NORT). The glucocorticoid receptor antagonist mifepristone and the beta-adrenoceptor antagonist propranolol were able to completely reverse the increased immobility time in the forced swimming test and the memory deficits in the NORT observed in MS rats. Our data support the hypothesis that elevated secretion of glucocorticoids may be associated to behavioural and cognitive deficits in MS rats. The stress hyperresponsiveness observed in MS rats could be attributed, at least in part, to an impaired feedback sensitivity mediated by hippocampal glucocorticoid receptors. It can also be suggested the possible involvement of the noradrenergic system in cognitive impairments mediated by glucocorticoids in the MS model.
Aisa
Bárbara
B
Department of Pharmacology, School of Medicine, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
Tordera
Rosa
R
Lasheras
Berta
B
Del Río
Joaquín
J
Ramírez
Maria J
MJ
D000223:Adaptation, Psychological / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology*; D003345:Corticosterone / Q000097:blood*; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003423:Critical Period, Psychological; D003863:Depression / Q000097:blood* / Q000209:etiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008426:Maternal Deprivation; D015735:Mifepristone / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012737:Sex Factors; D018709:Statistics, Nonparametric
D006727:Hormone Antagonists; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone; D009638:Norepinephrine