Asymmetry of the Endogenous Opioid System in the Human Anterior Cingulate: a Putative Molecular Basis for Lateralization of Emotions and Pain

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

来源：Cerebral Cortex, 2015, 25(1): 97-108.

DOI：10.1093/cercor/bht204

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

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.

• 出版日期2015-1