Abstract
The effects of long-term administration of opioid agonists on the regulation of prodynorphin gene expression in rat brain were investigated. Chronic intracerebroventricular treatment with the synthetic opioid agonist acting on the kappa receptor, U-50,488H, and the classic mu agonist morphine markedly decreased prodynorphin mRNA levels in hypothalamus, hippocampus and striatum of tolerant rats. Levels of ir-Dynorphin A remained unchanged except in two cases. Chronic exposure to opiates thus appears to induce modifications of the endogenous opioid system, as regards gene expression regulation.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
-
Analgesics / pharmacology
-
Animals
-
Blotting, Northern
-
Brain Chemistry / drug effects*
-
Corpus Striatum / drug effects
-
Corpus Striatum / metabolism
-
DNA Probes
-
Down-Regulation / drug effects*
-
Enkephalins / biosynthesis*
-
Enkephalins / genetics
-
Gene Expression Regulation / drug effects*
-
Hippocampus / drug effects
-
Hippocampus / metabolism
-
Hypothalamus / drug effects
-
Hypothalamus / metabolism
-
Male
-
Morphine / pharmacology
-
Narcotics / pharmacology*
-
Protein Precursors / biosynthesis*
-
Protein Precursors / genetics
-
Pyrrolidines / pharmacology
-
RNA, Messenger / biosynthesis
-
Rats
-
Rats, Inbred Strains
Substances
-
Analgesics
-
DNA Probes
-
Enkephalins
-
Narcotics
-
Protein Precursors
-
Pyrrolidines
-
RNA, Messenger
-
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
-
Morphine
-
preproenkephalin