Abstract: The prefrontal cortex (PFC) is known to play an important role not only in the regulation of emotion,
but in the integration of affective states with appropriate modulation of autonomic and neuroendocrine
stress regulatory systems. The present review highlights findings in the rat which helps to elucidate the
complex nature of prefrontal involvement in emotion and stress regulation. The medial PFC is
particularly important in this regard and while dorsomedial regions appear to play a suppressive role in
such regulation, the ventromedial (particularly infralimbic) region appears to activate behavioral,
neuroendocrine and sympathetic autonomic systems in response to stressful situations. This may be
especially true of spontaneous stress-related behavior or physiological responses to relatively acute
stressors. The role of the medial PFC is somewhat more complex in conditions involving learned
adjustments to stressful situations, such as the extinction of conditioned fear responses, but it is clear
that the medial PFC is important in incorporating stressful experience for future adaptive behavior. It is
also suggested that mesocortical dopamine plays an important adaptive role in this region by preventing
excessive behavioral and physiological stress reactivity. The rat brain shows substantial hemispheric
specialization in many respects, and while the right PFC is normally dominant in the activation of
stress-related systems, the left may play a role in countering this activation through processes of
interhemispheric inhibition. This proposed basic template for the lateralization of stress regulatory
systems is suggested to be associated with efficient stress and emotional self-regulation, and also to be
shaped by both early postnatal experience and gender differences.