Thus, acute withdrawal from drugs increases CRF in the central nucleus of the amygdala that has motivational significance for the anxiety-like effects of acute withdrawal and the increased drug intake associated with dependence (Figure 6). Acute withdrawal also may increase the release of norepinephrine in the bed nucleus of the stria terminalis and dynorphin in the nucleus accumbens, and both of which may contribute to the negative emotional state associated with dependence. Decreased activity of NPY in the central nucleus of the amygdala also may contribute to the anxiety-like state associated with ethanol dependence. Activation of brain stress systems (CRF, norepinephrine, dynorphin) combined with inactivation of brain anti-stress systems (NPY) elicits powerful emotional dysregulation in the extended amygdala. Such dysregulation of emotional processing may be a significant contribution to the between-system opponent processes that help maintain dependence and also set the stage for more prolonged state changes in emotionality such as protracted abstinence.
