A neurochemical yin and yang: does serotonin activate and norepinephrine deactivate the prefrontal cortex?

INTRODUCTION

The prefrontal cortex (PFC) receives serotonergic input from the dorsal raphe nucleus of the brainstem, as well as noradrenergic input from another brainstem nucleus, the locus coeruleus. A large number of studies have shown that these two neurotransmitter systems, and drugs that affect them, modulate the functional properties of the PFC in both humans and animal models.

RESULTS

Here I examine the hypothesis that serotonin (5-HT) plays a general role in activating the PFC, whereas norepinephrine (NE) plays a general role in deactivating this brain region. In this manner, the two neurotransmitter systems may have opposing effects on PFC-influenced behavior. To assess this hypothesis, three primary lines of evidence are examined comprising the effects of 5-HT and NE on impulsivity, cognitive flexibility, and working memory.

DISCUSSION

While all of the existing data do not unequivocally support the activation/deactivation hypothesis, there is a large body of support for it.