Lack of effect of chronic morphine treatment and naloxone-precipitated withdrawal on tyrosine hydroxylase, galanin, and neuropeptide Y mRNA levels in the rat locus coeruleus.
Morphine dependence was experimentally induced in rats by daily injection of increasing doses of morphine for seven days. Withdrawal was precipitated in half of the morphine-dependent rats by a single injection of naloxone on day 8. Behavioral signs of withdrawal were evident in the morphine/naloxone group. Gene expression in locus coeruleus (LC) neurons was investigated using quantitative in situ hybridization analysis. Messenger RNA (mRNA) levels for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and for precursors to galanin (GAL) and neuropeptide Y (NPY), peptides that coexist with norepinephrine in LC neurons, were not altered by chronic morphine treatment or naloxone-precipitated withdrawal. In contrast, mRNA levels for c-fos were dramatically elevated in the LC following naloxone-precipitated withdrawal. Chronic morphine treatment caused a small decrease in levels of mRNA encoding the precursor to corticotropin-releasing factor (CRF) in Barrington's nucleus. Although long-term adaptations of LC neurons have previously been implicated in the development of morphine tolerance, dependence, and withdrawal, alterations in the levels of TH, GAL, or NPY mRNA in the LC apparently do not underlie this process.
Holmes
P V
PV
Section on Behavioral Neuropharmacology, NIMH, Bethesda, Maryland 20892, USA.
de Bartolomeis
A
A
Koprivica
V
V
Crawley
J N
JN
D000818:Animals; D001345:Autoradiography; D019004:Galanin; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000009:adverse effects / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009478:Neuropeptide Y / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics*; D010455:Peptides / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D009478:Neuropeptide Y; D009479:Neuropeptides; D010455:Peptides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D009270:Naloxone; D009020:Morphine; D019004:Galanin; D014446:Tyrosine 3-Monooxygenase