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

Hiroyuki Watanabe, Sylvia Fitting, Muhammad Z. Hussain, Olga Kononenko, Anna Iatsyshyna, Takashi Yoshitake, Jan Kehr, Kanar Alkass, Henrik Druid, Henrik Wadensten, Per E. Andren, Ingrid Nylander, Douglas H. Wedell, Oleg Krishtal, Kurt F. Hauser, Fred Nyberg, Victor M. Karpyak, Tatjana Yakovleva, Georgy Bakalkin

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)97-108
Number of pages12
JournalCerebral Cortex
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Anterior cingulate cortex
  • Emotions
  • Endogenous opioid system
  • Lateralization
  • Pain

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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    Watanabe, H., Fitting, S., Hussain, M. Z., Kononenko, O., Iatsyshyna, A., Yoshitake, T., Kehr, J., Alkass, K., Druid, H., Wadensten, H., Andren, P. E., Nylander, I., Wedell, D. H., Krishtal, O., Hauser, K. F., Nyberg, F., Karpyak, V. M., Yakovleva, T., & Bakalkin, G. (2015). Asymmetry of the endogenous opioid system in the human anterior cingulate: A putative molecular basis for lateralization of emotions and pain. Cerebral Cortex, 25(1), 97-108. https://doi.org/10.1093/cercor/bht204