The enhanced CB1 function at CCK-GABAergic synapses hypothesis is reinforced by our observation that CMS-exposure facilitates induction of weak LTP. This effect is blocked by AM251 which indicates that not only is the LTP enhancement CB1-dependent but is also dependent on the release of eCBs. In non-stress related studies, hippocampal eCB signaling via CB1 is shown to prime LTP induction during either a DSI window (Carlson et al., 2002) or during long-term eCB-mediated suppression of CCK-GABAergic neurotransmission (Chevalyre and Castillo, 2004). Therefore, it is plausible that CMS-induced sensitization of GABAergic CB1 is a compensatory adaptation of the normal hippocampal eCB-LTP gating mechanism that would help to maintain optimal excitatory CA1 output during periods of compromised function (i.e. chronic stress). This gain in excitatory output may provide additional feedback to the HPA during stress (see discussion below) but would also allow increases in hippocampal-dependent cognitive function. One important caveat is that under a more intense LTP-induction protocol, we observed that LTP in stress slices is inhibited. This result agrees with studies showing that chronic stress in different forms impairs LTP in
