Tonic and phasic alteration in amygdala 5-HT, glutamate and GABA transmission after prefrontal cortex damage in rats.

The relationship between the ventromedial prefrontal cortex and the amygdala during the presentation of an unconditioned fear stimulus was assessed. Rats underwent bilateral ibotenic acid or vehicle administration into the ventromedial prefrontal cortex. Five weeks later, the behavior as well as the neurochemical changes in the amygdala was evaluated before and after a brief cat presentation. Lesioned animal freezing behavior increased 10 times when compared to controls. In the right basolateral amygdala, basal concentrations of 5-HT, 5-HIAA, glutamate and serine were elevated but basal level of GABA was diminished in lesioned animals relative to controls. Sham but not lesioned animals increased 5-HT and decreased GABA and serine levels after cat presentation. Phasic changes in glutamate were not detected either in lesioned or shams but the difference in amygdala glutamate between lesioned and shams persisted after cat presentation. These data show that increased serotonin and glutamate tone and decreased gabaergic tone in the amygdala correlate to elevated fear and anxiety after prefrontal cortex ibotenic acid lesion. The lesion also seems to produce a failure of adaptive changes in neurotransmitter systems revealing lost of control of the ventromedial prefrontal cortex over the amygdala in frightening situations.