Untitled

Stress-Induced Pathophysiology 249ing occurs in an environment or a context that is nonthreatening (e.g., if the dogis familiar, if one is among restrained or caged animals), then the prefrontal cortexhas the ability to override an inappropriate emotional response. Indeed, drawingfrom our example, Harari and colleagues (2003) have examined this type ofinteraction in humans using a functional imaging study. In this study, the subjectwas presented with a picture of a threatening object; as expected from other reports,this resulted in an activation of the amygdala. However, if the subject firstreceives verbal instructions regarding description or identification of objects inthe following picture, when the threatening picture is presented, the amygdala isnot activated. Instead, there is an activation of frontal cortical regions. This isconsistent with what would be predicted from our study of evoked neuronal responsesin anesthetized rodents.We have found that dopamine also exerts a potent regulatory influence overthe amygdala. Thus, dopamine was found to exert two effects over the responsesof basal/lateral amygdala neurons to stimuli. First, we observed that dopamineacting via D1 receptors increases the excitability and via D2 receptors increasesthe input resistance of pyramidal neurons in vitro (Kroner et al., 2005). This isconsistent with the observed increase in excitability following systemic administrationof dopamine D2 agonists in vivo (Rosenkranz & Grace, 2001). This translatesinto a greater amplitude of evoked response produced by stimulation ofsensory afferents to the basal/lateral amygdala complex (Rosenkranz & Grace,2001; Rosenkranz & Grace, 2002a). In contrast, activation of D1 receptors decreasesthe amplitude of the evoked IPSP observed in vivo upon stimulation ofprefrontal cortical afferents (Rosenkranz & Grace, 2002a). Therefore, in the presenceof dopamine, there is an increase in response to the sensory input and anattenuation in the ability of the prefrontal cortex to downregulate this response.In the case of normal activation of the dopamine system, as may occur during aheightened vigilance state, this would keep the organism attentive toward manystimuli that may otherwise be ignored. However, a hyperdopaminergic state mayresult in a pathological consequence. Thus, if there is too much dopamine stimulation,as may occur with amphetamine administration, the prefrontal cortex wouldlose its ability to attenuate normally benign stimuli, causing such stimuli to evoke amaximal emotional response. Therefore, even a familiar or nonthreatening stimulusmay cause the individual to respond with a strong fear response. Such a conditionwould also be present if the prefrontal cortex is incapable of normal activation,as may occur with schizophrenia. This exaggerated fear response to stimuli knownto be benign may represent a type of paranoia response in the subject.Central Medial Nucleus. The prefrontal cortex also exerts a potent regulatoryinfluence over the baseline activity and responsivity of neurons within the primaryautonomic output region of the amygdala, the central medial nucleus. Theinfluence of the prefrontal cortex was examined by testing the effects of transection