Proopiomelanocortin (POMC) mRNA expression: Distribution and region-specific down-regulation by chronic morphine in female guinea pig hypothalamus

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalMolecular Brain Research
Volume55
Issue number1
DOIs
StatePublished - Mar 30 1998

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Pro-Opiomelanocortin
Morphine
Hypothalamus
Guinea Pigs
Down-Regulation
Messenger RNA
Opioid Receptors
Placebos
Opiate Alkaloids
Middle Hypothalamus
Endorphins
Neurons
Complementary RNA
Median Eminence
Arcuate Nucleus of Hypothalamus
Opioid Peptides
RNA Precursors
Silver
In Situ Hybridization

Keywords

  • β-endorphin
  • Arcuate nucleus
  • Female guinea pig
  • In situ hybridization histochemistry
  • Median eminence
  • Morphine pellet

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

@article{1e6f0a6f9ae140b78c193789d83a08cd,
title = "Proopiomelanocortin (POMC) mRNA expression: Distribution and region-specific down-regulation by chronic morphine in female guinea pig hypothalamus",
abstract = "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.",
keywords = "β-endorphin, Arcuate nucleus, Female guinea pig, In situ hybridization histochemistry, Median eminence, Morphine pellet",
author = "Yuan Fang and Martin Kelly and Oline Ronnekleiv",
year = "1998",
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doi = "10.1016/S0169-328X(97)00348-3",
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volume = "55",
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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

AU - Ronnekleiv, Oline

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.

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