Elsevier

Brain Research

Volume 360, Issues 1–2, 23 December 1985, Pages 117-129
Brain Research

Autoradiographic distribution of Mu1 and Mu2 opioid binding in the mouse central nervous system

https://doi.org/10.1016/0006-8993(85)91227-2Get rights and content

Abstract

Several types of opioid binding sites have been differentiated using biochemical and pharmacological criteria. We have used quantitative in vitro autoradiography to compare the levels of mu1 and mu2 opiod binding in the mouse central nervous system. Mu1 sites have a high affinity for all labeled opioids studied to date and have been associated with their analgesic effects, whereas mu2 sites have a high affinity only for opiate alkaloids and have been associated with their respiratory depressant effects. We used [3H]dihydromorphine (DHM) to visualize total mu sites (mu1 and mu2) and [3H]DHM plus a low concentration of [d-Ala2-d-Leu5]enkephaline (DADL) to visualize mu2 sites. Levels of mu1 binding were determined by subtracting mu2 binding from total mu binding. This mu1 distribution was confirmed in selected regions by an alternate method using [3H]DADL.

High ratios of mu1 to mu2 binding were noted in frontal cortex, nucleus accumbens, rostral striatum, ventral pallidum, ventral periaqueductal gray matter, and laminae I and II of the spinal cord. The observation of high densities of mu1 binding in certain pain processing areas correlates with behavioral and pharmacological studies suggesting that analgesia from opiates and opioids is mediated primarily by mu1 sites. In other areas, such as the limbic system, dorsal nucleus of the vagus nerve, and nucleus of the solitary tract, eihter a low ratio of mu1 to mu2 binding or no mu1 binding was observed. This differential regional localization of mu1 and mu2 binding provides further evidence for the distinctnessof these sites.

Reference (60)

  • FrenkH.

    Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems

    Brain Res. Rev.

    (1983)
  • FrenkH. et al.

    The suppressant effects of naloxone on food and water intake in the rat

    Behav. Neural Biol.

    (1979)
  • GoodmanR.R. et al.

    Autoradiography of [3H]beta-endorphin binding in brain

    Brain Research

    (1983)
  • HoltzmanS.G.

    Effects of narcotic antagonists on fluid intake in rat

    Life Sci.

    (1975)
  • HughesJ.

    Isolation of an endogenous compound from the brain with pharmacologic properties similar to morphine

    Brain Research

    (1975)
  • LaubieM. et al.

    Action of the morphinomimetic agent, fentanyl on the nucleus tractus solitarii and the nucleus ambiguus cardiovascular neurons

    Eur. J. Pharmacol.

    (1980)
  • MorleyJ.E.

    Neuroendocrine effects of endogenous opioid peptides in human subjects: a review

    Psychoneuroendocrinol

    (1983)
  • PasternakG.W. et al.

    An endogenous morphine-like factor in mammalian brian

    Life Sci.

    (1975)
  • PrietoG.J. et al.

    N. raphe magnus lesions disrupt stimulation-produced analgesia from ventral but not dorsal midbrain areas

    Brain Research

    (1983)
  • UnnerstallJ.R. et al.

    Quantitative receptor autoradiography using [3H]Ultrofilm: application to multiple benzodiazepine receptors

    J. Neurosci. Methods

    (1982)
  • ZhangA.-Z. et al.

    Mu- and delta-opiate receptors: correlation with high and low affinity opiate binding sites

    Eur. J. Pharmacol.

    (1980)
  • BelluzziJ. et al.

    Enkephalins may mediate euphoria and drive-reduction reward

    Nature (London)

    (1977)
  • GillanM.G.C. et al.

    Comparison of the binding characteristics of tritiated opiates and opioid peptides

    Brit. J. Pharmacol.

    (1980)
  • GoldsteinA. et al.

    Dynorphin-(1–13), and extraordinarily potent opioid peptide

  • GoodmanR.R. et al.

    Light microscopic autoradiography of mu and delta opiate binding sites in mouse CNS

    Soc. Neurosci. Abstr.

    (1982)
  • GoodmanR.R. et al.

    Kappa opiate receptors localized by autoradiography to deep layers of cerebral cortex: relation to sedative effects

  • GoodmanR.R. et al.

    Differentiation of delta and mu opioid receptor localizations by light microscopic autoradiography

  • HewlettW.A. et al.

    Multiple opiate binding sites in rat brain: differential displacement of3H-naloxone binding by different opiate ligands

  • HoladayJ.W.

    Cardiovascular effects of endogenous opiate systems

    Ann. Rev. Pharmacol. Toxicol.

    (1983)
  • HoltzmanS.G.

    Behavioral effects of separate and combined administration of naloxone andd-amphetamine

    J. Pharmacol. Exp. Ther.

    (1974)
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