GABA(C) Receptors in the Lateral Amygdala: A Possible Novel Target for the Treatment of Fear and Anxiety Disorders?

Activation of GABA(A)Rs in the lateral nucleus of the amygdala (LA), a key site of plasticity underlying fear learning, impairs fear learning. The role of GABA(C)Rs in the LA and other brain areas is poorly understood. GABA(C)Rs could be an important novel target for pharmacological treatments of anxiety-related disorders since, unlike GABA(A)Rs, GABA(C)Rs do not desensitize. To detect functional GABA(C)Rs in the LA we performed whole cell patch clamp recordings in vitro. We found that GABA(A)Rs and GABA(B)Rs blockade lead to a reduction of evoked inhibition and an increase increment of excitation, but activation of GABA(C)Rs caused elevations of evoked excitation, while blocking GABA(C)Rs reduced evoked excitation. Based on this evidence we tested whether GABA(C)Rs in LA contribute to fear learning in vivo. It is established that activation of GABA(A)Rs leads to blockage of fear learning. Application of GABA(C) drugs had a very different effect; fear learning was enhanced by activating and attenuated by blocking GABA(C)Rs in the LA. Our results suggest that GABA(C) and GABA(A)Rs play opposing roles in modulation of associative plasticity in LA neurons of rats. This novel role of GABA(C)Rs furthers our understanding of GABA receptors in fear memory acquisition and storage and suggests a possible novel target for the treatment of fear and anxiety disorders.