Again, consistent with several previous studies (Misner and Sullivan, 1999; Nowicky et al., 1987; Collins et al., 1994, 1995; Terranova et al., 1995), pre-treatment with a CB1 agonist prevented LTP induction in non-stress animals. Our data also shows that pre-incubation with WIN inhibits LTP in stress animals. The commonly accepted mechanism for this cannabinoid-LTP block is the suppression of glutamate via CB1 activation and this reduction in glutamate leads to hypoactivation of AMPA and subsequently NMDA receptors (Misner and Sullivan, 1996). However, as we demonstrated, WIN application in CMS animals produces a net increase in excitatory neurotransmission via CB1-induced suppression of GABA release. We hypothesized that pre-incubation with WIN in stress slices would result in a LTP-like increase in excitatory neurotransmission that would occlude subsequent LTP induction. If this is the case, then pharmacologically removing more GABAergic inhibition should allow for additional plasticity. Indeed, blocking GABA(A) receptors with picrotoxin rescued LTP in slices from CMS animals. Interestingly, picrotoxin did not rescue LTP in non-stress slices even though blocking GABA did produce slightly-larger LTP in non-stress slices compared to normal non-stress
