Consistent with previous studies (Hoffman et al., 2006; Takahashi and Castillo, 2006) thirty minute application of WIN 55,212-5 (1 μM; WIN) produced a ~33% decrease in CA1 fEPSPs in slices from non-stress animals. Surprisingly, WIN application to slices from CMS-exposed animals resulted in a ~135% increase in fEPSPs (Fig 1a). A two-way repeated measures ANOVA (Group x Time) confirmed: 1) that following thirty minutes of WIN, the stress (134.96 ± 1.50%) and non-stress (67.08 ± 1.02%) groups were significantly different (F (1,16) = 972.31, p = 0.000) and 2) that WIN significantly altered fEPSP responses in both groups compared to baseline responses (F (1,16) = 530.60, p = 0.000). To confirm the WIN effects were due to CB1 activation, a subset of slices from both stress and non-stress animals were pre-incubated (>1 hr) and continuously perfused with 3 μM AM251. During WIN application, AM251 prevented both the WIN-induced increase (134.96 ± 1.50% vs. 103.52 ± 2.20%; t (16) = 18.48, p = 0.000) in stress slices and the WIN-induced decrease in non-stress slices (67.08 ± 1.02% vs. 100.64 ± 1.37%; t (16) = 15.06, p = 0.000) (Fig 1b).
