Studies by Pistis et al., using extracellular single-unit recordings, explored the effect of CB1 receptor activation on the spontaneous activity of BLA principal neurons and local GABAergic interneurons within the BLA (Pistis et al., 2004). Administration of the CB1 receptor agonist HU-210 decreased BLA interneuron spike frequency, an effect reversed by the CB1 receptor antagonists AM251 and SR141716. Win 55212-2 had a bi-phasic effect in interneuron firing rate, as a low dose (0.125 mg/kg i.v.) stimulated firing, while higher doses (0.5–1 mg/kg i.v.) inhibited firing. Both effects blocked by the CB1 receptor antagonists AM251 and SR141716. Furthermore, both Win 55212-2 and HU-210 inhibited firing rate of antidromically identified BLA projection neurons. This effect of Win 55212-2 was reversed by the CB1 receptor antagonist SR141716 and the vanilloid receptor antagonist capsazepine, but not the CB1 receptor antagonist, AM251 (Pistis et al., 2004). Interestingly, AM251 not only failed to reverse the inhibitory effect of Win 55212-2, it actually strongly potentiated it. Neither SR141716 nor AM251 administered alone affected BLA projection neuron firing rate (Pistis et al., 2004).
