The effects of morphine treatment and morphine withdrawal on the dynorphin and enkephalin systems in Sprague-Dawley rats.
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 neurointermediate lobe were 0ven lower in the withdrawal state.(ABSTRACT TRUNCATED AT 250 WORDS)
Nylander
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I
Department of Clinical Neuroscience, Drug Dependence Research, Karolinska Institute, Stockholm, Sweden.
Vlaskovska
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M
Terenius
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L
D000704:Analysis of Variance; D000818:Animals; D004361:Drug Tolerance; D004399:Dynorphins / Q000032:analysis*; D004723:Endorphins / Q000032:analysis*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000032:analysis*; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D010455:Peptides / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D004723:Endorphins; D010455:Peptides; D009270:Naloxone; D004743:Enkephalin, Leucine; D004399:Dynorphins; C026768:enkephalin-Leu, Arg(6)-; D009020:Morphine; C036200:rimorphin