Linked Life Data

10651883

Source:http://linkedlifedata.com/resource/pubmed/id/10651883

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-3-16
pubmed:abstractText
To study the consequences of impaired functioning of the glucocorticoid receptor (GR) for behavioural, neuroendocrine and neurochemical responses to a psychological stressor, a transgenic mouse expressing antisense RNA against GR was used. Previous studies on these transgenic mice have shown that impairment of GR evolves in disturbed neuroendocrine regulation and certain behavioural responses to stress. Here we investigated putative disturbances on the level of brain neurotransmission in GR-impaired (GR-i) mice using an in vivo microdialysis method. Through a microdialysis probe in the hippocampus, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and free corticosterone [as an index of hypothalamic-pituitary-adrenocortical (HPA) axis activity] were monitored. Moreover, specific behaviours (e.g. grooming, eating/drinking, sniffing, nest building and locomotion) displayed by the mice during collection of the dialysates were scored. Measurement of dialysate concentrations of corticosterone on days 1 and 3 after insertion of the microdialysis probe showed that the free levels of this glucocorticoid were significantly lower in GR-i mice toward the evening. On day 2 after insertion of the microdialysis probe, baseline values of dialysate corticosterone, 5-HT and 5-HIAA were assessed, after which mice were exposed to a rat placed into their home cage. The rat and mouse were separated by a Plexiglas wall. A positive correlation between baseline hippocampal extracellular levels of 5-HT and 5-HIAA and the time spent performing active behaviours was observed in both genotypes. The main active behaviour performed at the baseline was grooming behaviour. During the rat exposure period, control mice remained mostly sitting and/or lying with their eyes fixed on the rat. Moreover, they showed a profound rise in free corticosterone levels. In contrast, GR-i mice displayed significantly more activities along the separation wall and a trend toward more grooming behaviour, but no increase of free corticosterone. In both mouse lines, exposure to a rat increased hippocampal extracellular levels of 5-HT and 5-HIAA. The rise in 5-HT was, however, more pronounced in the GR-i mice. From these data it may be concluded that life-long GR impairment has profound consequences for behavioural and neuroendocrine responses to a psychological stressor. Moreover, long-term impaired functioning of GR evolves in hyper-responsiveness of the raphe-hippocampal serotonergic system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
283-91
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10651883-Animals, pubmed-meshheading:10651883-Behavior, Animal, pubmed-meshheading:10651883-Corticosterone, pubmed-meshheading:10651883-Drinking Behavior, pubmed-meshheading:10651883-Feeding Behavior, pubmed-meshheading:10651883-Grooming, pubmed-meshheading:10651883-Hippocampus, pubmed-meshheading:10651883-Hydroxyindoleacetic Acid, pubmed-meshheading:10651883-Hypothalamo-Hypophyseal System, pubmed-meshheading:10651883-Male, pubmed-meshheading:10651883-Mice, pubmed-meshheading:10651883-Mice, Inbred Strains, pubmed-meshheading:10651883-Mice, Transgenic, pubmed-meshheading:10651883-Microdialysis, pubmed-meshheading:10651883-Motor Activity, pubmed-meshheading:10651883-Pituitary-Adrenal System, pubmed-meshheading:10651883-Promoter Regions, Genetic, pubmed-meshheading:10651883-RNA, Antisense, pubmed-meshheading:10651883-Rats, pubmed-meshheading:10651883-Receptors, Glucocorticoid, pubmed-meshheading:10651883-Serotonin, pubmed-meshheading:10651883-Stress, Psychological, pubmed-meshheading:10651883-Time Factors
pubmed:year
2000
pubmed:articleTitle
Glucocorticoid receptor impairment alters CNS responses to a psychological stressor: an in vivo microdialysis study in transgenic mice.
pubmed:affiliation
Max Planck Institute of Psychiatry, Section Neuropsychopharmacology, Kraepelinstrasse 2, D-80804 Munich, Germany. linthors@mpipsykl.mpg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't