RT Journal Article
SR Electronic
T1 Decreases in Endogenous Opioid Peptides in the Rat Medullo-Coerulear Pathway after Chronic Morphine Treatment
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8659
OP 8666
DO 10.1523/JNEUROSCI.20-23-08659.2000
VO 20
IS 23
A1 Elisabeth J. Van Bockstaele
A1 James Peoples
A1 A. Sue Menko
A1 Kirk McHugh
A1 Guy Drolet
YR 2000
UL http://www.jneurosci.org/content/20/23/8659.abstract
AB Several biochemical changes have been described in noradrenergic neurons of the locus coeruleus (LC) after chronic morphine treatment. Changes in neurochemical expression in opioid afferent projections to the LC may be equally important in modulating noradrenergic neurons during chronic opiate exposure. To test the hypothesis that opioid peptides in LC afferents are altered after chronic opiate administration, we exposed adult male rats to either morphine or placebo pellets for 5 d. Tissue sections through the LC were processed for peroxidase or gold–silver labeling of methionine5-enkephalin (met-ENK) and analyzed using light or electron microscopy, respectively. Light level densitometry and ultrastructural analysis showed that there was a significant decrease in immunolabeling for ENK in LC-afferent terminals of morphine-treated rats. Western immunoblot analysis confirmed that protein levels for both leucine5- and methionine5-ENK were significantly decreased in tissue samples containing the LC after chronic morphine treatment. To test whether decreases in ENK protein expression were mirrored by decreases in gene expression, Northern blot analysis of preproenkephalin (PPE) mRNA was conducted in tissue samples obtained through the medulla, a brainstem area that contains the major opioid afferents to the LC. PPE mRNA was reduced in samples obtained from morphine-treated rats. Finally, in situ hybridization experiments confirmed significant decreases in PPE mRNA expression in the nucleus paragigantocellularis, a region known to provide a robust opioid input to the LC. These data suggest that there is a decrease in the synthesis of the opioid peptide mRNA and protein in the medullo-coerulear pathway after chronic exposure to morphine. Such alterations in opioid peptide levels during opiate dependence may contribute to the observed hyperactivity of LC neurons during opiate withdrawal.