TY - JOUR
T1 - Proopiomelanocortin (POMC) mRNA expression
T2 - Distribution and region-specific down-regulation by chronic morphine in female guinea pig hypothalamus
AU - Fang, Yuan
AU - Kelly, Martin J.
AU - Rønnekleiv, Oline K.
N1 - Funding Information:
This study was supported by NIH grants DA07165, DA05158, and DA00192 (RSDA to MJK). We would like to thank Dr. Peter J. Fuller for his generous gift of POMC cDNA plasmid, and also thank Martha Bosch, Barry Naylor and Matthew J. Cunningham for their helpful assistance with experiments.
PY - 1998/3/30
Y1 - 1998/3/30
N2 - There is compelling evidence that endogenous opioid peptides are regulated by exogenous opiates. Our previous studies have shown that the μ-opioid receptor protein and mRNA are down-regulated in the mediobasal hypothalamus of the female guinea pig following chronic morphine treatment. In addition, electrophysiological studies have shown that hypothalamic β-endorphin (β-EP) neurons express μ-opioid receptors that are uncoupled and down-regulated following chronic morphine treatment. Currently, we tested the hypothesis that chronic morphine, which produces down-regulation of μ-opioid receptors, causes a down-regulation of pro-opiomelanocortin (POMC, the precursor of β-EP) mRNA expression in female guinea pig hypothalamus. Female guinea pigs were ovariectomized and implanted subcutaneously (s.c.) with 4 x 75 mg pellets for 2 days plus six more pellets of either morphine (n = 6) or placebo (n = 6) for another 5 days. Animals were sacrificed between 1000 and 1100 h on day 7. The expression of POMC mRNA were investigated using in situ hybridization histochemistry with a guinea pig specific 35S-labeled cRNA probe in hypothalamic tissue sections. POMC mRNA was localized to the arcuate nucleus (Arc) and median eminence (ME) of the medial basal hypothalamus. The distribution pattern was the same in both morphine and placebo control animals. However, the density of silver grains was less in morphine treated animals versus placebo control animals. Overall, the level of POMC mRNA was decreased by 22% in the Arc of morphine-treated guinea pigs as compared with the placebo controls (p < 0.05). This decrease in POMC mRNA expression was even greater in the caudal Arc (28%, p < 0.01) in morphine-treated animals. These results suggested that the biosynthetic activity of POMC neurons is down-regulated with chronic exposure to morphine.
AB - There is compelling evidence that endogenous opioid peptides are regulated by exogenous opiates. Our previous studies have shown that the μ-opioid receptor protein and mRNA are down-regulated in the mediobasal hypothalamus of the female guinea pig following chronic morphine treatment. In addition, electrophysiological studies have shown that hypothalamic β-endorphin (β-EP) neurons express μ-opioid receptors that are uncoupled and down-regulated following chronic morphine treatment. Currently, we tested the hypothesis that chronic morphine, which produces down-regulation of μ-opioid receptors, causes a down-regulation of pro-opiomelanocortin (POMC, the precursor of β-EP) mRNA expression in female guinea pig hypothalamus. Female guinea pigs were ovariectomized and implanted subcutaneously (s.c.) with 4 x 75 mg pellets for 2 days plus six more pellets of either morphine (n = 6) or placebo (n = 6) for another 5 days. Animals were sacrificed between 1000 and 1100 h on day 7. The expression of POMC mRNA were investigated using in situ hybridization histochemistry with a guinea pig specific 35S-labeled cRNA probe in hypothalamic tissue sections. POMC mRNA was localized to the arcuate nucleus (Arc) and median eminence (ME) of the medial basal hypothalamus. The distribution pattern was the same in both morphine and placebo control animals. However, the density of silver grains was less in morphine treated animals versus placebo control animals. Overall, the level of POMC mRNA was decreased by 22% in the Arc of morphine-treated guinea pigs as compared with the placebo controls (p < 0.05). This decrease in POMC mRNA expression was even greater in the caudal Arc (28%, p < 0.01) in morphine-treated animals. These results suggested that the biosynthetic activity of POMC neurons is down-regulated with chronic exposure to morphine.
KW - Arcuate nucleus
KW - Female guinea pig
KW - In situ hybridization histochemistry
KW - Median eminence
KW - Morphine pellet
KW - β-endorphin
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U2 - 10.1016/S0169-328X(97)00348-3
DO - 10.1016/S0169-328X(97)00348-3
M3 - Article
C2 - 9645954
AN - SCOPUS:0032579762
SN - 0169-328X
VL - 55
SP - 1
EP - 8
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1
ER -