LACK OF EFFECT OF CHRONIC MORPHINE TREATMENT AND NALOXONE-PRECIPITATED WITHDRAWAL ON TYROSINE-HYDROXYLASE, GALANIN, AND NEUROPEPTIDE-Y MESSENGER-RNA LEVELS IN THE RAT LOCUS-COERULEUS

Morphine dependence was experimentally induced in rats by daily inject ion of increasing doses of morphine for seven days, Withdrawal was pre cipitated 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) n eurons was investigated using quantitative in situ hybridization analy sis. Messenger RNA (mRNA) levels for tyrosine hydroxylase (TH), the ra te-limiting enzyme in catecholamine synthesis, and for precursors to g alanin (GAL) and neuropeptide Y (NPY), peptides that coexist with nore pinephrine in LC neurons, were not altered by chronic morphine treatme nt or naloxone-precipitated withdrawal. In contrast, mRNA levels for c -fos were dramatically elevated in the LC following naloxone-precipita ted withdrawal. Chronic morphine treatment caused a small decrease in levels of mRNA encoding the precursor to corticotropin-releasing facto r (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 T H, GAL, or NPY mRNA in the LC apparently do not underlie this process. (C) 1995 Wiley-Liss, Inc.