Despite functioning as a LTP gating mechanism, CB1 via exogenous activation also inhibits LTP induction (Nowicky et al., 1987; Collins et al., 1994, 1995; Terranova et al., 1995; Misner and Sullivan, 1999). This inhibition is thought to underlie learning and memory impairments caused by marijuana use (Nowicky et al., 1987; Terranova et al., 1995). Thus, we pre-incubated slices in WIN (1 μM) to test if exogenous CB1 activation prior to our weak TBS would also impair LTP in both stress and non-stress animals. In the continuous presence of WIN, LTP was blocked in both stress and non-stress slices (103.20 ± 1.8% and 96.73 ± 0.68%, respectively, Fig. 5a and 5b). Next, these experiments were repeated in the presence of picrotoxin to determine the relative contribution of glutamate-CB1 and GABA-CB1 to the WIN-LTP inhibition. Since blocking GABAergic neurotransmission results in enhanced LTP (Wigström and Gustafsson, 1986), we used a relatively weak concentration of PTX (50 μM) to partially block GABA(A) receptors and to mimic CB1-mediated suppression of neurotransmission. Application of PTX prevented the WIN block of LTP in stress slices (159.57
