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Mu-opioid receptors are involved in the tolerance to nicotine antinociception

Lola Galeote1, Brigitte L Kieffer, Rafael Maldonado

  • 1Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain. rafael.maldonado@upf.edu

Journal of Neurochemistry
|March 17, 2006
PubMed

Insights

Mu-opioid receptors are involved in nicotine tolerance. While their density changed in some brain areas, their spinal cord activity increased, suggesting a complex role in developing tolerance to nicotine

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • The endogenous opioid system influences nicotine's effects on pain and addiction.
  • Understanding the role of specific opioid receptors, like mu-opioid receptors, is crucial for elucidating nicotine's mechanisms of action.

Purpose of the Study:

  • To investigate the involvement of mu-opioid receptors in the development of tolerance to nicotine's antinociceptive effects.
  • To explore adaptive changes in mu-opioid receptor expression and function following chronic nicotine exposure.

Main Methods:

  • Chronic nicotine administration to C57BL/6 mice to induce tolerance.
  • Autoradiography using [(3)H]DAMGO to assess mu-opioid receptor density.
  • Guanosine [(35)S]5'-(gamma-thio)-triphosphate ([(35)S]GTPgammaS) binding assays to measure receptor functional activity.
  • Evaluation of nicotine-induced antinociception in mu-opioid receptor knockout mice.

Main Results:

  • Chronic nicotine treatment led to tolerance in the tail-immersion test.
  • Mu-opioid receptor density decreased in the caudate-putamen and nucleus accumbens but remained unchanged in the spinal cord.
  • Functional activity of spinal mu-opioid receptors significantly increased after nicotine treatment.
  • Tolerance to nicotine's antinociceptive effects developed faster in mu-opioid receptor knockout mice compared to wild-type.

Conclusions:

  • Mu-opioid receptors play a significant role in the development of tolerance to nicotine's antinociceptive effects.
  • Adaptive changes in mu-opioid receptor function, particularly in the spinal cord, contribute to nicotine tolerance.
  • The absence of mu-opioid receptors accelerates the development of nicotine tolerance, highlighting their modulatory role.

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