Whose side are you on: Does serotonin preferentially activate the right hemisphere and norepinephrine the left?

Abstract

Serotonin (5-HT) and norepinephrine (NE) innervate both the left and right hemispheres of the brain, but whether they affect lateralization of function is unknown. This paper concisely examines evidence that these two neurotransmitters differentially affect the two hemispheres, and puts forth the novel hypothesis 5-HT preferentially activates the right hemisphere (RH) and NE the left hemisphere (LH). The principal lines of evidence comprise studies of: (1) 5-HT and NE level measurement, (2) receptor binding, (3) functional brain imaging, (4) dichotic listening, and (5) electroencephalography and evoked potentials. In assessing these 5 lines, emphasis is placed on studies of pharmaceutical drugs that affect the 5-HT and NE systems. While all of the data do not support the hypothesis, they are generally consistent with it, or a variant of the hypothesis that there is a bias toward 5-HT preferentially activating a majority of brain areas or functions in the RH, and NE a majority of LH areas or functions. If this hypothesis, or a variant of it, is correct, it may be relevant to understanding the physiological basis of neuropsychiatric disorders that could involve dysfunction in brain monoaminergic systems, as well as understanding potential lateralization of the effects of drugs that act on these systems.