The effects of morphine treatment and morphine withdrawal on the dynorphin and enkephalin systems in Sprague-Dawley rats

• Published in: Psychopharmacology Vol. 118; no. 4; p. 391
• Main Authors: Nylander, I, Vlaskovska, M, Terenius, L
• Format: Journal Article
• Language: English
• Published: Germany 01.04.1995
• Subjects: Analysis of Variance; Animals; Drug Tolerance; Dynorphins - analysis; Endorphins - analysis; Enkephalin, Leucine - analogs & derivatives; Enkephalin, Leucine - analysis; Male; Morphine - administration & dosage; Morphine - adverse effects; Naloxone - pharmacology; Peptides - analysis; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome - metabolism
• ISSN: 0033-3158
• DOI: 10.1007/BF02245939

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.