Alternatively, it has been shown, in isolated rat BLA neurons, that late phase DSI is mediated by metabotropic glutamate receptor-5-driven eCB release, not calcium-mediated eCB release (Zhu and Lovinger, 2005). These data raise the possibility that repeated stress could be enhancing the receptor-driven late component of DSI, which is not present under control conditions. This could occur by an eCB ‘priming’ phenomenon which has recently been described by Alger and co-workers (Edwards et al, 2008). In hippocampal neurons, DSI can be enhanced by prior activation of group-1 metabotropic glutamate receptors. It is possible that repeated restraint stress progressively ‘primes’ neurons in vivo, and this priming is measurable ex vivo several hours later as enhanced late DSI.
