In line with this, immediate early-gene studies have found that systemic administration of a CB1 receptor antagonist increases the neuronal activation of the BLA in unstressed animals (Singh et al., 2004; Patel et al., 2005b), supporting the hypothesis that endocannabinoid signaling tonically inhibits excitatory transmission in the BLA. Given that the primary source of excitatory inputs to BLA projection neurons are cortical and thalamic afferents transmitting sensory information regarding external conditions (Sah et al., 2003: McDonald, 1992), CB1 receptor activation within the BLA likely attenuates HPA axis activity by gating excitatory sensory input afferents to the BLA, and subsequently dampens the firing rate of BLA projection neurons which exert trans-synaptic relays to the PVN. This hypothesis is in agreement with recent transgenic data demonstrating that endocannabinoid regulation of HPA axis responsivity is governed by CB1 receptors on principal forebrain neurons, but not GABAergic interneurons (Steiner et al., 2008b).
