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Eur J Pharmacol. 1996 Apr 22;301(1-3):19-25.

Antisense to the glucocorticoid receptor in hippocampal dentate gyrus reduces immobility in forced swim test.

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Department of Animal Physiology, University of Groningen, Haren, Netherlands.


Immobility time of rats in the forced swim test was reduced after bilateral infusion of an 18-mer antisense phosphorothioate oligodeoxynucleotide targeted to the glucocorticoid receptor mRNA into the dentate gyrus of the hippocampus. Vehicle-, sense- and scrambled sequence-treated animals spent significantly more time immobile than antisense-treated animals during the initial test. Immunolabeling of the glucocorticoid receptor in brain sections demonstrated a reduced expression of glucocorticoid receptor proteins in antisense-treated dentate gyrus compared to the contralateral sense-treated dentate gyrus or contralateral scrambled sequence-treated dentate gyrus. During the initial test the time spent on immobility was also reduced when rats were treated with the glucocorticoid receptor antagonist RU38486 (17 beta-hydroxy-11 beta-(4-dimethylamino-phenyl)17 alpha-(1-propnyl)estra-4,9-diene-3-one)) 6 h (but not 1 h) earlier. These results demonstrate the participation of glucocorticoid receptors in the expression of immobility in a forced swim test during the initial test.

[Indexed for MEDLINE]

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