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

• Lateralization of 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 m-, d- and k-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 five “classical” neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg and Met-enkephalin-Arg-Phe, preferential d-/m- and k-/m-opioid agonists demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B strongly correlated with Leu-enkephalin-Arg in the left but not right ACC suggesting different mechanisms of conversion of this k-opioid agonist to d-/m-opioid ligand in the two hemispheres; in the right ACC dynorphin 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 underlyes in part lateralization of higher functions including positive and negative emotions and pain in the human brain.

Ämnesord

Medical and Health Sciences  (hsv)

Basic Medicine  (hsv)

Neurosciences  (hsv)

Medicin och hälsovetenskap  (hsv)

Medicinska grundvetenskaper  (hsv)

Neurovetenskaper  (hsv)

Neuroscience  (uu)

Neurovetenskap  (uu)

Nyckelord

Anterior Cingulate Cortex

Lateralization

Endogenous Opioid System

Emotions

Pain