Endocannabinoid (eCB) activation of CB1 is capable of facilitating LTP induction during both short-term (Carlson et al., 2002) and long-term (Chevaleyre and Castillo, 2004) eCB-mediated suppression of CCK-GABAergic neurotransmission. Since our earlier findings suggest that CMS enhances CB1-mediated suppression of inhibition by exogenous activation, we hypothesized that CMS would lead to enhanced LTP induction. To test this idea, we used a weak Theta-Burst Stimulation protocol (Chevaleyre and Castillo, 2004) that resulted in non-saturating, low-level LTP (~125% of baseline) in a preliminary study with non-stress control animals. When delivered to a separate cohort of CMS (n=18) and non-stress animals (n=15), the weak TBS produced significantly greater LTP in stress compared to non-stress animals (174.47 ± 1.8% vs. 134.31 ± 1.28%; F (1, 28) = 245.64, p = 0.000, Fig. 4a). In the presence of AM251 (3 μM), TBS still produced significant LTP compared to baseline (125.21 ± 1.8%, p = 0.001, paired t-test) in slices from stress animals; however, as illustrated in Fig 4b, this LTP was significantly lower than in non-AM251 treated slices (p = 0.000, student’s t-test). These observations
