Elsevier

Neuroscience Letters

Volume 383, Issues 1–2, 22–29 July 2005, Pages 141-144
Neuroscience Letters

The α2-adrenoceptor antagonist yohimbine reduces glial fibrillary acidic protein upregulation induced by chronic morphine administration

https://doi.org/10.1016/j.neulet.2005.04.002Get rights and content

Abstract

Previous literature data show prominent interactions between α2-adrenoceptor ligands and opioid drugs, however, the nature of such interactions is still largely unknown. In the present study, we aimed to examine the potential protective effect of yohimbine, a α2-adrenoceptor antagonist, against glial fibrillary acidic protein (GFAP) alterations elicited by chronic morphine treatment. Increased astrogliosis, as indicated by increased GFAP immunohistochemical staining, was observed in the ventral tegmental area, nucleus accumbens shell, and frontal cortex of chronic morphine-treated (10 mg kg−1, i.p., every 12 h for 13 days) rats compared with those treated with saline. Pretreatment with yohimbine (2 mg kg−1, i.p., 30 min before each morphine injection) provided protection against morphine-induced GFAP upregulation. The present study demonstrates that yohimbine pretreatment reduces long-term morphine exposure-induced alterations in the astroglial reaction, suggesting that α2-adrenergic mechanisms may play an important role in mediating morphine-induced pathological effects in the brain.

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Acknowledgements

We thank Linda Hamalainem for her help in the preparation of the manuscript. This study was supported by grants from Laboratorios ESTEVE, Agencia Antidroga CAM and Plan Nacional sobre Drogas.

References (31)

  • L.F. Alguacil et al.

    Alpha-2 adrenoceptor ligands and opioid drugs: pharmacological interactions of therapeutic interest

    Curr. Neuropharmacol.

    (2004)
  • D. Beitner-Johnson et al.

    Chronic morphine impairs axoplasmic transport in the rat mesolimbic dopamine system

    NeuroReport

    (1993)
  • M.A. Boronat et al.

    Attenuation of tolerance to opioid-induced antinociception and protection against morphine-induced decrease of neurofilament proteins by idazoxan and other I2-imidazoline ligands

    Br. J. Pharmacol.

    (1998)
  • A.O.S. El-Kadi et al.

    The influence of chronic treatment with clonidine, yohimbine and idazoxan on morphine withdrawal

    Psychopharmacology

    (1997)
  • L.F. Eng et al.

    Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000)

    Neurochem. Res.

    (2000)
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