GLUCOCORTICOID RECEPTOR ACTIVATION LOWERS THE THRESHOLD FOR NMDA-RECEPTOR-DEPENDENT HOMOSYNAPTIC LONG-TERM DEPRESSION IN THE HIPPOCAMPUS THROUGH ACTIVATION OF VOLTAGE-DEPENDENT CALCIUM CHANNELS

The effects of the glucocorticoid receptor agonist RU-28362 on homosyn aptic long-term depression (LTD) were examined in hippocampal slices o btained from adrenal-intact adult male rats. Field excitatory postsyna ptic potentials were evoked by stimulation of the Schaffer collateral/ commissural pathway and recorded in stratum radiatum of area CA1. Low- frequency stimulation (LFS) was delivered at LTD threshold (2 bouts of 600 pulses, 1 Hz, at baseline stimulation intensity). LFS of the Scha ffer collaterals did not produce significant cant homosynaptic LTD in control slices. However, identical conditioning in the presence of the glucocorticoid receptor agonist RU-28362 (10 mu M) produced a robust LTD, which vias blocked by the selective glucocorticoid antagonist RU- 38486. The LTD induced by glucocorticoid receptor activation was depen dent on N-methyl-D-aspartate (NMDA) receptor activity, because the spe cific NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) blocked the facilitation. However, the facilitation of LTD was not due to a potentiation of the isolated NMDA receptor potential by RU-28362. The facilitation of LTD by RU-28362 was also blocked by coin cubation of the L-type voltage-dependent calcium channel (VDCC) antago nist nimodipine. Selective activation of the L-type VDCCs by the agoni st Bay K 8644 also facilitated LTD induction. Both nimodipine and D-AP 5 were effective in blocking the facilitation of LTD by Bay K 8644. Th ese results indicate that L-type VDCCs can contribute to NMDA-receptor -dependent LTD induction.