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

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.