GABA receptors inhibited by benzodiazepines mediate fast inhibitory transmission in the central amygdala

The amygdala is intimately involved in emotional behavior, and its role in the generation of anxiety and conditioned fear is well known. Benzodiazepin es, which are commonly used for the relief of anxiety, are thought to act b y enhancing the action of the inhibitory transmitter GABA. We have examined the properties of GABA-mediated inhibition in the amygdala. Whole-cell rec ordings were made from neurons in the lateral division of the central amygd ala. Application of GABA evoked a current that reversed at the chloride equ ilibrium potential. Application of the GABA antagonists bicuculline or SR95 531 inhibited the GABA-evoked current in a manner consistent with two bindi ng sites. Stimulation of afferents to neurons in the central amygdala evoke d an IPSC that was mediated by the release of GABA. The GABA(A) receptor an tagonists bicuculline and picrotoxin failed to completely block the IPSC. T he bicuculline-resistant IPSC was chloride-selective and was unaffected by GABA(B)-receptor antagonists. Furthermore, this current was insensitive to modulation by general anesthetics or barbiturates. In contrast to their act ions at GABA(A) receptors, diazepam and flurazepam inhibited the bicucullin e-resistant IPSC in a concentration-dependent manner. These effects were fu lly antagonized by the benzodiazepine site antagonist Ro15-1788. We conclud e that a new type of ionotropic GABA receptor mediates fast inhibitory tran smission in the central amygdala. This receptor may be a potential target f or the development of new therapeutic strategies for anxiety disorders.