Exposure to various forms of chronic stress alters CB1 receptor expression and signalling in several brain regions including the hippocampus, hypothalamus, prefrontal cortex, ventral striatum, nucleus accumbens and amygdala (Hill et al., 2008b; Reich et al., 2009; Hill et al., 2005; Wamsteeker et al., 2010; Rossi et al., 2008; Wang et al., 2010; Patel at al., 2009; Sumislawski et al., 2011). The present study investigated the effects of CMS, a model of depression, on hippocampal CB1 physiology. We observed several novel findings: 1) exogenous activation of CB1 by WIN (1 μM) in stress animals resulted in a ~135% increase in excitatory neurotransmission, whereas CB1 activation in non-stress animals leads to a ~30% decrease in glutamatergic neurotransmission, 2) during blockade of GABA(A) neurotransmission, CB1 activation yielded a ~35% decrease in stress animals, 3) induction of weak LTP is enhanced in CMS-exposed animals compared to controls and this enhancement is CB1 dependent and 4) the LTP-blocking property of WIN shifts from being glutamate-dependent in non-stress animals to being GABA-dependent in stress animals.
