Journal
CEREBRAL CORTEX
Volume 25, Issue 1, Pages 97-108Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bht204
Keywords
anterior cingulate cortex; emotions; endogenous opioid system; lateralization; pain
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Funding
- Swedish Council for Working Life and Social Research (FAS)
- Swedish Science Research Council (VR)
- Swedish Research Council FORMAS
- Swedish Institute (Visby Program)
- NIH [NIH K02 DA027374]
- NATIONAL INSTITUTE ON DRUG ABUSE [K02DA027374] Funding Source: NIH RePORTER
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Lateralization of the processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria, and pain, the mu-, delta-, and kappa-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and 5 classical neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg (LER) and Met-enkephalin-Arg-Phe, preferential delta-/mu- and kappa-/mu-opioid agonists, demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B (Dyn B) strongly correlated with LER in the left, but not in the right ACC suggesting different mechanisms of the conversion of this kappa-opioid agonist to delta-/mu-opioid ligand in the 2 hemispheres; in the right ACC, Dyn B may be cleaved by PACE4, a proprotein convertase regulating left-right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlies in part lateralization of higher functions, including positive and negative emotions and pain in the human brain.
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