Inhibition of the Amygdala: Key to Pathological States?

The amygdala plays an important role in associating sensory stimuli with aversive or appetitive outcomes. Conditioning procedures potentiate inputs to the amygdala, which facilitate emotional responses via subcortical and cortical outputs. Powerful inhibitory circuits exist that control expression of conditioned responses in the amygdala, including inhibition from prefrontal cortex. Deficient inhibitory tone in the amygdala could lead to overexpression of conditioned responses, producing pathological states such as anxiety disorders and drug-seeking behavior. Support for this comes from several lines of animal research: (1) GABA antagonist-induced priming of anxiety states, (2) extinction of conditioned fear, (3) modulation of inhibitory avoidance memory, and (4) cue-induced reinstatement of drug seeking. Cue-induced craving in humans is associated with feelings of fear and autonomic arousal, suggesting a link between fear and addiction in the amygdala. Future therapies aimed at increasing inhibitory tone in the amygdala, either locally or via the prefrontal cortex, may prevent anxiety disorders and addiction relapse. Novel neuropeptides, which can either excite or inhibit specific components of anxiety responses, offer promise in this regard.