, Volume 213, Issue 2, pp 171–182

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


DOI: 10.1007/s00213-010-1856-1

Cite this article as:
Fitzgerald, P.J. Psychopharmacology (2011) 213: 171. doi:10.1007/s00213-010-1856-1



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.


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.


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


Executive functionImpulsivityCognitive flexibilityReversal learningWorking memoryFluoxetineClonidinePropranololGuanfacine

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.The Zanvyl Krieger Mind/Brain Institute, Solomon H. Snyder Department of NeuroscienceJohns Hopkins UniversityBaltimoreUSA
  2. 2.National Institute on Alcohol Abuse and Alcoholism (NIAAA)BethesdaUSA