Several studies have investigated the effects of cannabinoid signaling on amygdalar neuocircuitry in vivo. Pistis et al. studied the effect of systemically administered CB1 receptor agonists on the activity of nucleus accumbens neurons receiving monosynaptic inputs from BLA projection neurons, using single-unit extracellular recordings (Pistis et al., 2002). Stimulation currents were adjusted such that 50% of the stimuli delivered to the BLA (at 1 Hz) resulted in an action potential in the nucleus accumbens neuron being recorded. Systemic administration of the CB1 receptor agonists Win 55212-2, HU-210, and THC all decreased BLA-stimulation evoked spike probability in nucleus accumbens neurons, an effect reversed by the CB1 receptor antagonist SR141716, which when administered alone, had no effect (Pistis et al., 2002). These data suggest that CB1 receptor activation modulates glutamate release from BLA projection neurons, likely at the level of axon terminals that innervate target structures such as the nucleus accumbens.
