title: Asymmetry of the endogenous opioid system in the human anterior cingulate: a putative molecular basis for lateralization of emotions and pain.
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.
authors: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences.
authors: Hiroyuki
authors: H
authors: Watanabe
authors: Department of Pharmacology and Toxicology.
authors: Sylvia
authors: S
authors: Fitting
authors: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences.
authors: Muhammad Z
authors: MZ
authors: Hussain
authors: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences Key State Laboratory, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
authors: Olga
authors: O
authors: Kononenko
authors: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences Department of Human Genetics, Institute of Molecular Biology and Genetics, Kyiv, Ukraine.
authors: Anna
authors: A
authors: Iatsyshyna
authors: Pharmacological Neurochemistry, Department of Physiology and Pharmacology.
authors: Takashi
authors: T
authors: Yoshitake
authors: Pharmacological Neurochemistry, Department of Physiology and Pharmacology.
authors: Jan
authors: J
authors: Kehr
authors: Forensic Medicine, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors: Kanar
authors: K
authors: Alkass
authors: Forensic Medicine, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors: Henrik
authors: H
authors: Druid
authors: Medical Mass Spectrometry, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors: Henrik
authors: H
authors: Wadensten
authors: Medical Mass Spectrometry, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors: Per E
authors: PE
authors: Andren
authors: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences.
authors: Ingrid
authors: I
authors: Nylander
authors: Department of Psychology, University of South Carolina, Columbia, USA and.
authors: Douglas H
authors: DH
authors: Wedell
authors: Key State Laboratory, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
authors: Oleg
authors: O
authors: Krishtal
authors: Department of Pharmacology and Toxicology Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA, USA.
authors: Kurt F
authors: KF
authors: Hauser
authors: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences.
authors: Fred
authors: F
authors: Nyberg
authors: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors: Victor M
authors: VM
authors: Karpyak
authors: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences.
authors: Tatjana
authors: T
authors: Yakovleva
authors: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences.
authors: Georgy
authors: G
authors: Bakalkin
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism; D004644:Emotions / Q000502:physiology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018847:Opioid Peptides / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
chemical_list: D018847:Opioid Peptides; D012333:RNA, Messenger
keywords: anterior cingulate cortex; emotions; endogenous opioid system; lateralization; pain
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