Rapid changes in the content of proenkephalin A and corticotrophin releasing hormone mRNAs in the paraventricular nucleus during morphine withdrawal in urethane-anaesthetized rats.
Quantitative in situ hybridization was used to measure corticotrophin-releasing hormone (CRH) and proenkephalin A mRNA in the medial parvocellular paraventricular nucleus (PVN) 4 h after test procedures. Urethane anaesthesia alone resulted in a significant increase in both CRH and proenkephalin transcripts. The additional stimulus of i.p. hypertonic saline, however, resulted in a further significant increase in both mRNA species. Female rats were given intracerebroventricular (i.c.v.) infusion for 5 days of either morphine sulphate to induce tolerance and dependence, or vehicle, via a subcutaneous osmotic minipump implanted under ether anaesthesia. The rats were then anaesthetized with urethane, fitted with an intravenous cannula for injections and 65 min later either naloxone (5 mg/kg) or vehicle was injected. Naloxone alone in the i.c.v. vehicle rats had no effect on CRH or proenkephalin A mRNA. In i.c.v. morphine-infused rats proenkephalin a mRNA in the PVN was significantly less than in controls. Naloxone given to i.c.v. morphine-infused rats resulted in a doubling of hybridization to proenkephalin mRNA in the PVN which was significantly greater than that seen in the i.c.v. vehicle group. CRH mRNA in the PVN was not altered either by naloxone in control rats, or by chronic i.c.v. morphine infusion. By contrast, naloxone did increase CRH mRNA by ca. 40% in morphine-infused rats. The results show that stress-induced increases in CRH and enkephalin mRNAs in the PVN do not require conscious appreciation of the stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Harbuz
M
M
Department of Physiology, University Medical School, Edinburgh, U.K.
Russell
J A
JA
Sumner
B E
BE
Kawata
M
M
Lightman
S L
SL
D000768:Anesthesia, General; D000818:Animals; D001345:Autoradiography; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D004745:Enkephalins / Q000235:genetics*; D015870:Gene Expression; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D015345:Oligonucleotide Probes; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology / Q000503:physiopathology*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013462:Sulfur Radioisotopes; D014520:Urethane
D004745:Enkephalins; D015345:Oligonucleotide Probes; D011498:Protein Precursors; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; C029992:proenkephalin; D014520:Urethane; D009020:Morphine; D003346:Corticotropin-Releasing Hormone