Effects of morphine treatment on pro-opiomelanocortin systems in rat brain.
In previous studies to determine whether chronic opiate administration might negatively feedback upon endogenous opioid systems in the CNS, investigators found no changes in steady-state concentrations of opioid peptides following morphine pelleting. However, since only steady-state levels were measured, it was still not clear whether morphine treatment altered the release and/or biosynthesis of opioid-containing neurons. The goal of the present study was to assess the effects of chronic morphine pelleting on the dynamics of beta-endorphin (beta E) biosynthesis in rats. Hence, at several times during a 7-day morphine treatment, concentrations of total beta E-immunoreactivity (-ir), as well as chromatographically sieved forms of beta E, were determined by RIA, and mRNA levels of pro-opiomelanocortin (POMC) were measured by a solution phase protection assay using a mouse or rat POMC 32P-labelled riboprobe. Concentrations of total beta E-ir or different forms of beta E-ir peptides (i.e. beta-lipotropin, beta E1-31, or beta E1-27/beta E1-26) in the hypothalamus or midbrain following either 1 or 7 days of treatment were similar in morphine- and placebo-pelleted animals. However, a significant increase in total hypothalamic beta E-ir was observed following 3 days of morphine pelleting; chromatographic analyses indicated that this was primarily due to a selective increase in the opiate inactive forms of beta E, i.e. beta E1-27/beta E1-26. After 7 days of pelleting, morphine-treated animals tended to have lower POMC mRNA levels than those of placebo controls (20 to 50% decrease in different studies). The accumulation of hypothalamic beta E-ir at 3 days, and the apparent decline in POMC mRNA levels at 7 days, lend support to the hypothesis that morphine negatively feeds back upon POMC neurons in the brain by inhibiting beta E release and biosynthesis.
Bronstein
D M
DM
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0720.
Przewlocki
R
R
Akil
H
H
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004343:Drug Implants; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D001615:beta-Endorphin / Q000096:biosynthesis
D004343:Drug Implants; D012333:RNA, Messenger; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D009020:Morphine