The role of glutamate and gamma-aminobutyric acid in fear extinction: Clinical implications for exposure therapy

Although much is now known about the neural basis of fear acquisition, the mechanisms of fear inhibition or suppression remain largely obscure. Fear inhibition is studied in the laboratory through the use of an extinction procedure, in which an animal (typically a rat) is exposed to nonreinforced presentations of a conditioned stimulus (CS; e.g., a light or tone) that had previously been paired with a fear-inducing unconditioned stimulus (US; e.g., a mild footshock). Over the course of such training, the conditioned fear response exhibited by the rat in the presence of the CS is reduced in amplitude and frequency. This procedure is analogous to those employed in the treatment of fear dysregulation in humans, which typically involve exposure to the feared object in the absence of any overt danger. Recent work on the neural basis of extinction indicates that the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate are critically involved. Gamma-aminobutyric acid may act to inhibit brain areas involved in fear learning (e.g., the amygdala), and glutamate, acting at N-methyl-D-aspartate receptors, may play a role in the neural plasticity that permits this GABA-mediated inhibition to be exerted appropriately. These insights have significant implications for the conduct of extinction-based clinical interventions for fear disorders. (C) 2002 Society of Biological Psychiatry.