Downregulation of brain mineralocorticoid and glucocorticoid receptor by antisense oligodeoxynucleotide treatment fails to alter spatial navigation in rats

Adult male Brown Norway rats were long-term intracerebroventricularly (i.c. v.) infused with antisense oligodeoxynucleotides (18-mer, double endcapped phosphorothioate protected) targeting either mineralocorticoid or glucocort icoid receptor mRNA, or received the respective mixed bases sequence or veh icle. Mineralocorticoid receptor-mixed bases and glucocorticoid receptor-mi xed bases oligodeoxynucleotide infusion (1 mu g/0.5 mu l/h) over a time per iod of seven days did not alter hippocampal mineralocorticoid receptor and glucocorticoid receptor binding when compared to vehicle treatment. In cont rast, i.c.v. administration of mineralocorticoid receptor, as well as gluco corticoid receptor-antisense over the same time period resulted in a signif icantly reduced binding of mineralocorticoid receptor and glucocorticoid re ceptor in the hippocampus [mineralocorticoid receptor-antisense group appro x. 72% of mineralocorticoid receptor-mixed bases and vehicle groups (100%); glucocorticoid receptor antisense group approx. 77% of glucocorticoid rece ptor-mixed bases and vehicle]. The specificity of these antisense effects i s indicated by the finding that rats treated with mineralocorticoid recepto r-antisense did not show any changes in glucocorticoid receptor and vice ve rsa. Animals treated according to this infusion protocol and tested in the Morris water maze for their spatial navigation abilities failed to show sig nificant differences among the groups. These data indicate that a reduction of hippocampal mineralocorticoid receptor or glucocorticoid receptor bindi ng capacity by 20-30% does not interfere with spatial navigation. (C) 1998 Elsevier Science B.V. All rights reserved.