Format

Send to

Choose Destination
Cereb Cortex. 2015 Jan;25(1):97-108. doi: 10.1093/cercor/bht204. Epub 2013 Aug 19.

Asymmetry of the endogenous opioid system in the human anterior cingulate: a putative molecular basis for lateralization of emotions and pain.

Author information

1
Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences.
2
Department of Pharmacology and Toxicology.
3
Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences Key State Laboratory, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
4
Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences Department of Human Genetics, Institute of Molecular Biology and Genetics, Kyiv, Ukraine.
5
Pharmacological Neurochemistry, Department of Physiology and Pharmacology.
6
Forensic Medicine, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
7
Medical Mass Spectrometry, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
8
Department of Psychology, University of South Carolina, Columbia, USA and.
9
Key State Laboratory, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
10
Department of Pharmacology and Toxicology Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA, USA.
11
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.

Abstract

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 μ-, δ-, and κ-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 δ-/μ- and κ-/μ-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 κ-opioid agonist to δ-/μ-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.

KEYWORDS:

anterior cingulate cortex; emotions; endogenous opioid system; lateralization; pain

PMID:
23960211
PMCID:
PMC4259275
DOI:
10.1093/cercor/bht204
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center