TRANSMITTER SYSTEMS INVOLVED IN NEURAL PLASTICITY UNDERLYING INCREASED ANXIETY AND DEFENSE - IMPLICATIONS FOR UNDERSTANDING ANXIETY FOLLOWING TRAUMATIC STRESS

Lasting changes in anxiety-like behavior (ALB) may be produced in seve ral ways. These include partial limbic kindling, injection of the beta -carboline FG-7142, and brief, non-injurious, exposure of rodents to c ats (predator stress). Both seizures and FG-7142 induce long-term pote ntiation (LTP) in efferent pathways of the amygdala known to participa te in feline defensive behavior. By comparing the behavioral and physi ological effects of partial kindling and injection of FG-7142, NMDA-de pendent LTP in the right amygdalo-periacqueductal gray (PAG) pathway e merges as being critical to maintained increases in feline ALB. A simi lar dependence on NMDA-mediated processes is described for lasting inc reases in rodent ALB following predator stress. The lasting aftereffec ts of predator stress on a variety of measures parallel many of the sy mptoms of past-traumatic stress disorder (PTSD). Support is provided f or the idea that behavioral changes following FG-7142 and predator str ess may model anxiety associated with PTSD. Moreover, it is suggested that both models share mechanisms in common involving the PAG. These m echanisms likely involve initiation of LTP by NMDA receptors, and prol ongation of LTP by CCKB receptors. To the extent that response to the stressors reviewed here mimics the symptoms of PTSD, the data implicat e NMDA-mediated processes in the creation of what van der Kolk has cal led permanent emotional memories in PTSD. Their representation may be in the form of NMDA-dependent LTP of transmission within the amygdala and between the amygdala and its efferents. CCK may play a pivotal rol e in prolonging limbic LTP and anxiety following traumatic stress. Sin ce block of CCKB receptors before and after the stressor prevents last ing increases in ALB, pharmacological intervention to block CCK recept ors shortly after a traumatic stressor might be efficacious in mitigat ing the permanence of these emotional memories. (C) 1997 Elsevier Scie nce Ltd.