PMID- 7749752 OWN - NLM STAT- MEDLINE DCOM- 19950622 LR - 20190614 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 672 IP - 1-2 DP - 1995 Feb 20 TI - Long-term exposure to opioid antagonists up-regulates prodynorphin gene expression in rat brain. PG - 42-7 AB - We investigated the effect of long-term administration of opioid antagonists on the regulation of prodynorphin gene expression in rat brain. Intracerebroventricular (i.c.v.) injections for seven days of nor-binaltorphimine (nor-BNI), the highly selective kappa opioid antagonist, naloxone and its longer acting analog naltrexone, both relatively selective antagonists for the mu opioid receptor, markedly raised prodynorphin mRNA levels in rat hypothalamus, hippocampus and striatum. Peptides, namely immunoreactive-dynorphin A (ir-dyn A), were unaffected after chronic treatment with all antagonists, in the same tissues. These results, taken together with our previous observations, suggest that chronic opioid antagonists, acting on kappa and mu opioid receptors, clearly up-regulate prodynorphin gene expression in discrete rat brain regions, activating its biosynthesis. Moreover, our data support the hypothesis that the endogenous opioid system plays a role in the mechanisms underlying the development of opiate tolerance. FAU - Romualdi, P AU - Romualdi P AD - Department of Pharmacology, University of Bologna, Italy. FAU - Lesa, G AU - Lesa G FAU - Donatini, A AU - Donatini A FAU - Ferri, S AU - Ferri S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Enkephalins) RN - 0 (Narcotic Antagonists) RN - 0 (Protein Precursors) RN - 36B82AMQ7N (Naloxone) RN - 36OOQ86QM1 (norbinaltorphimine) RN - 5S6W795CQM (Naltrexone) RN - 93443-35-7 (preproenkephalin) SB - IM MH - Animals MH - Brain/*physiology MH - Enkephalins/*genetics MH - Gene Expression/*drug effects MH - Male MH - Naloxone/pharmacology MH - Naltrexone/analogs & derivatives/pharmacology MH - Narcotic Antagonists/*pharmacology MH - Protein Precursors/*genetics MH - Rats MH - Rats, Sprague-Dawley MH - Time Factors EDAT- 1995/02/20 00:00 MHDA- 1995/02/20 00:01 CRDT- 1995/02/20 00:00 PHST- 1995/02/20 00:00 [pubmed] PHST- 1995/02/20 00:01 [medline] PHST- 1995/02/20 00:00 [entrez] AID - 0006-8993(94)01379-V [pii] AID - 10.1016/0006-8993(94)01379-v [doi] PST - ppublish SO - Brain Res. 1995 Feb 20;672(1-2):42-7. doi: 10.1016/0006-8993(94)01379-v.