Repeated restraint-induced modulation of long-term potentiation in the dentate gyrus of the mouse.

We studied the potential for induction of long-term potentiation (LTP) in slices of the dentate gyrus of C57BL/6 mouse, prepared 24h after 1, 3, 7, 14 or 21 successive daily neck restraint sessions lasting for 10min. In slices from control animals and mice restrained only once, LTP (155+/-2% of baseline) was evident for at least 2h, but LTP was impaired after 3 sessions of neck restraint. This effect could be blocked by administration of the glucocorticoid receptor (GR) antagonist RU38486 before each restraint. One day after 3 restraint sessions the levels of plasma corticosterone, GR and mineralocorticoid receptor (MR) proteins remained elevated. After 7 neck restraint sessions the LTP level returned to normal; after 14 and 21 restraint sessions LTP was enhanced. LTP enhancement after 14 daily restraint sessions was not blocked by the GR antagonist RU38486 administered before each restraint; the MR antagonist RU28318 blocked LTP induction completely. After 14 daily restraint sessions the level of GR and MR proteins did not differ from the control and the plasma corticosterone level remained slightly elevated. These data indicate that repeated stress imposed by brief neck restraint bidirectionally modulates the potential for LTP in the dentate gyrus in a manner dependent on the number of daily restraint sessions.