The involvement of mineralocorticoid receptors in the effects of repeated brief restrain stress on LTP in the dentate gyrus of mice
Increased level of corticoid hormons during stress results in activation of hippocampal mineralocorticosteroid receptors (MRs) and glucocorticoid receptors (GRs). Our earlier studies showed impairment of LTP in the dentate gyrus (DG) of mice after 3 daily sessions of brief (10 min) restraint stress and LTP augmentation after 14 and 21 daily sessions of immobilization. In contrast, 1 and 7 daily sessions of immobilization did not affect LTP level. We demonstrated that the GR antagonist RU38486 selectively blocks the effect of 3 sessions of restraint. In the present study we investigated whether the effects of repeated brief restraint stress are mediated by MRs. C57BL/6 male mice were exposed to the restraint, lasting 10 minutes, for 3 and 14 days. 1 hour before immobilization the animals were subcutaneously injected with the MR receptor antagonist spironolactone. Mice were sacrifi ced 24 h after the last exposure to restraint and hippocampal slices were prepared. Field excitatory postsynaptic potentials were evoked by the stimulation of the lateral perforant path and recorded from the molecular layer of the DG. LTP induction was attempted by applying 4 trains of high-frequency stimulation (HFS, 100 Hz, 1 s, repeated every 25 s). In both experimental groups immediately after HFS recorded responses were potentiated but 2 h later they were diminished relative to control. Thus, the present results show that spironolactone blocks LTP induction after 3 and 14 days of daily restraint.