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The effects of morphine treatment and morphine withdrawal on the dynorphin and enkephalin systems in sprague-dawley rats

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Abstract

The effect of morphine tolerance and withdrawal on prodynorphin peptides was studied in relevant brain areas and in the pituitary gland of male Sprague-Dawley rats, and compared with effects on the proenkephalin-derived peptide Met-enkephalin. After 8 days of morphine injections (twice daily), dynorphin A and B levels increased in the nucleus accumbens and dynorphin A levels increased also in the striatum. Morphine treatment increased striatal Met-enkephalin. Leu-enkephalinArg6 levels were reduced in the ventral tegmental area (VTA). Morphine-treated rats had very low Leu-enkephalinArg6 levels in the hippocampus as compared to saline control rats. Comparison of the relative amounts of dynorphin peptides and the shorter prodynorphin-derived peptides, Leu-enkephalinArg6 and Leu-enkephalin, revealed a relative increase in dynorphin peptides versus shorter fragments in the nucleus accumbens, VTA and hippocampus. Morphine-tolerant rats had lower levels of dynorphin A in both lobes of the pituitary gland, whereas hypothalamic dynorphin levels were unaffected by morphine. Leu-enkephalinArg6 levels were reduced in the hypothalamus, but not changed in the pituitary gland. Naloxone-precipitated withdrawal accentuated the increase in dynorphin A and B levels in the accumbens and dynorphin A levels in the striatum, while inducing an increase in enkephalin levels in the accumbens and Met-enkephalin in the VTA. In the hippocampus, Leu-enkephalinArg6 levels remained low in the withdrawal state. The low dynorphin levels in the anterior part of the pituitary gland were reversed by naloxone, whereas the low dynorphin A levels in the neurointer-mediate lobe were even lower in the withdrawal state. In conclusion, morphine tolerance and withdrawal affected prodynorphin-derived peptides in areas related to central reward mechanisms, and in the pituitary gland. The dynorphin peptides and the LeuenkephalinArg6 fragment were not affected similarly, indicating an effect also on metabolic interconversion.

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  1. Department of Clinical Neuroscience, Drug Dependence Research Section, Karolinska Institute, S-171 76, Stockholm, Sweden

    I. Nylander, M. Vlaskovska & L. Terenius

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  1. I. Nylander
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  2. M. Vlaskovska
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  3. L. Terenius
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Nylander, I., Vlaskovska, M. & Terenius, L. The effects of morphine treatment and morphine withdrawal on the dynorphin and enkephalin systems in sprague-dawley rats. Psychopharmacology 118, 391–400 (1995). https://doi.org/10.1007/BF02245939

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  • DOI: https://doi.org/10.1007/BF02245939

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