Elsevier

Neuroscience

Volume 72, Issue 3, June 1996, Pages 767-783
Neuroscience

Differential messenger RNA expression of prodynorphin and proenkephalin in the human brain

https://doi.org/10.1016/0306-4522(96)00002-4Get rights and content

Abstract

The opiate system is involved in a wide variety of neural functions including pain perception, neuroendocrine regulation, memory, drug reward, and tolerance. Such functions imply that endogenous opioid peptides should have anatomical interactions with limbic brain structures believed to be involved in the experience and expression of emotion. Using in situ hybridization histochemistry, the messenger RNA expression of the opioid precursors, prodynorphin and proenkephalin, was studied in whole hemisphere human brain tissue. Different components of the limbic system were found to be characterized by a high gene expression of either prodynorphin or proenkephalin messenger RNA. Brain regions traditionally included within the limbic system (e.g. amygdala, hippocampus, entorhinal cortex and cingulate cortex) as well as limbic-associated regions including the ventromedial prefrontal cortex and patch compartment of the neostriatum showed high prodynorphin messenger RNA expression. In contrast, high levels of proenkephalin messenger RNA were more widely expressed in the hypothalamus, periaqueductal gray, various mesencephalic nuclei, bed nucleus of the stria terminalis, and ventral pallidum; brain regions associated with endocrine-reticular-motor continuum of the limbic system.

The marked anatomical dissociation between the expression of these two opioid peptide genes, seen clearly in whole hemisphere sections, indicates that distinct functions must be subserved by the prodynorphin and proenkephalin systems in the human brain.

References (86)

  • L. Heimer et al.

    Ventral striatum and ventral pallidum. Components of the motor systems?

    Trends Neurosci.

    (1982)
  • T.E. Helton et al.

    Convulsant doses of cocaine alter immediate early gene and opioid peptide expression in rat limbic forebrain

    Molec. Brain Res.

    (1993)
  • Y.L. Hurd et al.

    Cocaine self-administration differentially alters mRNA expression of striatal peptides

    Molec. Brain Res.

    (1992)
  • Y.L. Hurd et al.

    Neuropeptide compartmentalization within the human neostriatum: in situ hybridization and in vitro autoradiography characterization

    Neuroscience

    (1995)
  • E.D. Kemble et al.

    Effects of eltoprazine hydrochloride on exploratory behavior and social attraction in mice

    Pharmac. Biochem. Behav.

    (1991)
  • H. Khachaturian et al.

    Prodynorphin peptide immunocytochemistry in rhesus monkey brain

    Peptides

    (1985)
  • W. Lasón et al.

    The effects of excitatory amino acids on proenkephalin and prodynorphin mRNA levels in the hippocampal dentate gyrus of the rat; an in situ hybridization study

    Molec. Brain Res.

    (1992)
  • C.M. Leonard et al.

    Neurons in the amygdala of monkey with responses selective for faces

    Behav. Brain Res.

    (1985)
  • M.E. Lewis et al.

    Anatomical relationship between opioid peptides and receptors in rhesus monkey brain

    Brain Res. Bull.

    (1984)
  • P.G.M. Luiten et al.

    The hypothalamus, intrinsic connections and outflow pathways to the endocrine system in relation to the control of feeding and metabolism

    Prog. Neurobiol.

    (1987)
  • A. Mansour et al.

    κ1 receptor mRNA distribution in the rat CNS: comparison to κ receptor binding and prodynorphin mRNA

    Molec. cell. Neurosci.

    (1994)
  • A. Mansour et al.

    Delta opioid receptor mRNA distribution in the brain—comparison to delta receptor binding and proenkephalin mRNA

    J. Chem. Neuroanat.

    (1993)
  • R. Maurer et al.

    Multiple opiate receptor in human brain: an autoradiographic investigation

    Life Sci.

    (1983)
  • J.F. McGinty

    Prodynorphin immunoreactivity is located in different neurons than proenkephalin immunoreactivity in the cerebral cortex of rats

    Neuropeptides

    (1985)
  • G.J. Mogenson et al.

    From motivation to action: functional interface between the limbic system and the motor system

    Prog. Neurobiol.

    (1980)
  • B.J. Morris et al.

    Dopaminergic regulation of striatal proenkephalin mRNA and prodynorphin mRNA: contrasting effects of D1 and D2 antagonists

    Neuroscience

    (1988)
  • A.P. Nisbet et al.

    Preproenkephalin and preprotachykinin messenger RNA expression in normal human basal ganglia and in Parkinson's disease

    Neuroscience

    (1995)
  • E.P.J. Pioro et al.

    Loss of substance P and enkephalin immunoreactivity in the human substantia nigra after striato-pallidal infarction

    Brain Res.

    (1984)
  • R. Quirion et al.

    Distribution of multiple opioid receptors in the human brain

  • C.D. Ramsdell et al.

    Expression of prodynorphin-derived peptides and mRNA in guinea-pig cortex

    Neuropeptides

    (1993)
  • S. Reimer et al.

    Differential dopaminergic regulation of proenkephalin and prodynorphin mRNAs in the basal ganglia of rats

    Molec. Brain Res.

    (1992)
  • S. Vincent et al.

    Immunohistochemical evidence for a dynorphin immunoreactive striatonigral pathway

    Eur. J. Pharmacol.

    (1982)
  • J.P. Aggleton

    The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction

    (1993)
  • R. Albin et al.

    Preproenkephalin messenger RNA-containing neurons in striatum of patients with symptomatic and presymptomatic Huntington's disease: an in situ hybridization study

    Ann. Neural.

    (1991)
  • S.E. Arnold et al.

    Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia

    Archs gen. Psychiat.

    (1991)
  • R. Bals-Kubik et al.

    Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preferences paradigm in rats

    J. Pharm. exp. Ther.

    (1992)
  • A. Bechara et al.

    Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans

    Science

    (1995)
  • H. Beckman et al.

    Prenatal disturbances of nerve cell migration in the entorhinal region: a common vulnerability factor in functional psychoses?

    J. neural Transm.

    (1991)
  • J.D. Beluzzi et al.

    Enkephalin may mediate euphoria and drive reward

    Nature

    (1977)
  • H. Braak et al.

    Neurofibrillary changes confined to the entorhinal region and an abundance of cortical amyloid in cases of presenile and senile dementia

    Acta neuropath.

    (1990)
  • H. Braak et al.

    Neuropathological staging of Alzheimer-related changes

    Acta neuropath.

    (1991)
  • S. Brené et al.

    Expression of mRNAs encoding ARPP-16/19, ARPP-21 and DARPP-32 in human brain tissue

    J. Neurosci.

    (1994)
  • P. Broca

    Anatomie comparee circonvolutions cérébrales: le grand lobe limbique et la scissure limbique dans la série des mammifères

    Rev. Anthropol.

    (1878)
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