In stress animals, Glutamatergic-CB1 activation was isolated from GABAergic-CB1 activation by continuously treating slices with the GABA(A) antagonist, picrotoxin (100 μM; PTX). During these experiments, application of WIN in the presence of PTX yielded a significant decrease in fEPSP slope (56.87 ± 1.56%, p = 0.001, t-test) compared to baseline responses, whereas AM251 prevented this decrease (105.00 ± 1.56%, p = 0.08; Fig 2). These observations suggest that CB1 physiology at CA1 glutamatergic synapses is not affected by CMS exposure. However, the data permit the hypothesis that CMS sensitizes GABAergic CB1 physiology resulting in a WIN-induced decrease in CCK-GABAergic neurotransmission and a net gain in excitatory neurotransmission. A summary of the WIN experiments is provided in Figure 3a. Note that these experiments were performed in slices (~2–3 per animal) prepared from the same cohort of stress (n=20) and non-stress (n= 12) animals.
