Altered gene expression and functional activity of opioid receptors in the cerebellum of CB1 cannabinoid receptor knockout mice after acute treatments with cannabinoids

Estera Páldyová, E. Bereczki, M. Sántha, T. Wenger, A. Borsodi, S. Benyhe

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Numerous studies have shown functional links between the cannabinoid and opioid systems. The goal of this study was to evaluate whether acute treatments by endogenous cannabinoid agonist, selective CB1 or CB2 receptor antagonists modulate the expression of μ-(MOR) and δ-(DOR) opioid receptor mRNA levels and functional activity in the cerebellum of transgenic mice deficient in the CB1 type of cannabis receptors. We examined the effect of noladin ether (endogenous cannabinoid agonist) pretreatment on MOR and DOR mRNA expression by using reverse transcription and real-time polimerase chain reaction (PCR) and the ability of subsequent application of the opioid agonists to activate G-proteins, as measured by [ 35S]GTPγS binding, in wild-type (CB1 +/+) and CB1 cannabinoid receptor deficient (CB1 -/-, 'knockout', K.O.) mice. The acute administration of noladin ether markedly reduced MOR-mediated G-protein activation and caused a significant increase in the level of MOR mRNAs in the cerebella of wild-type, but not in the CB1 -/- mice. No significant differences were observed in DOR functional activity and mRNA expression in wild-type animals. In CB1 -/- mice the expression of DOR mRNA increased after noladin ether treatment, but no changes were found in DOR functional activity. In addition, Rimonabant (selective central cannabinoid CB1 receptor antagonist) and SR144528 (selective peripheral cannabinoid CB2 receptor antagonist) caused significant potentiation in MOR functional activity in the wild-type animals, whereas DOR mediated G-protein activation was increased in the CB1 -/- mice. In contrast, Rimonabant and SR144528 decreased the MOR and DOR mRNA expressions in both CB1 +/+ and CB1 -/- mice. Taken together, these results indicate that acute treatment with cannabinoids causes alterations in MOR and DOR mRNA expression and functional activity in the cerebella of wild-type and CB1 knockout mice indicating indirect interactions between these two signaling systems.

Original languageEnglish
Pages (from-to)113-129
Number of pages17
JournalActa Biologica Hungarica
Volume58
Issue numberSUPPL. 1
DOIs
Publication statusPublished - Nov 2007

Fingerprint

cannabinoids
Cannabinoid Receptor CB1
Cannabinoids
narcotics
Opioid Receptors
cerebellum
Gene expression
Knockout Mice
ether
Cerebellum
gene expression
rimonabant
Gene Expression
Messenger RNA
receptors
protein
mice
G-proteins
GTP-Binding Proteins
Cannabinoid Receptor Antagonists

Keywords

  • [S]GTPγS binding
  • Cannabinoid receptors
  • CB receptor knockout mouse
  • Cerebellum
  • Noladin ether
  • Opioid receptors
  • Real-time PCR
  • Rimonabant
  • SR144528

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

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title = "Altered gene expression and functional activity of opioid receptors in the cerebellum of CB1 cannabinoid receptor knockout mice after acute treatments with cannabinoids",
abstract = "Numerous studies have shown functional links between the cannabinoid and opioid systems. The goal of this study was to evaluate whether acute treatments by endogenous cannabinoid agonist, selective CB1 or CB2 receptor antagonists modulate the expression of μ-(MOR) and δ-(DOR) opioid receptor mRNA levels and functional activity in the cerebellum of transgenic mice deficient in the CB1 type of cannabis receptors. We examined the effect of noladin ether (endogenous cannabinoid agonist) pretreatment on MOR and DOR mRNA expression by using reverse transcription and real-time polimerase chain reaction (PCR) and the ability of subsequent application of the opioid agonists to activate G-proteins, as measured by [ 35S]GTPγS binding, in wild-type (CB1 +/+) and CB1 cannabinoid receptor deficient (CB1 -/-, 'knockout', K.O.) mice. The acute administration of noladin ether markedly reduced MOR-mediated G-protein activation and caused a significant increase in the level of MOR mRNAs in the cerebella of wild-type, but not in the CB1 -/- mice. No significant differences were observed in DOR functional activity and mRNA expression in wild-type animals. In CB1 -/- mice the expression of DOR mRNA increased after noladin ether treatment, but no changes were found in DOR functional activity. In addition, Rimonabant (selective central cannabinoid CB1 receptor antagonist) and SR144528 (selective peripheral cannabinoid CB2 receptor antagonist) caused significant potentiation in MOR functional activity in the wild-type animals, whereas DOR mediated G-protein activation was increased in the CB1 -/- mice. In contrast, Rimonabant and SR144528 decreased the MOR and DOR mRNA expressions in both CB1 +/+ and CB1 -/- mice. Taken together, these results indicate that acute treatment with cannabinoids causes alterations in MOR and DOR mRNA expression and functional activity in the cerebella of wild-type and CB1 knockout mice indicating indirect interactions between these two signaling systems.",
keywords = "[S]GTPγS binding, Cannabinoid receptors, CB receptor knockout mouse, Cerebellum, Noladin ether, Opioid receptors, Real-time PCR, Rimonabant, SR144528",
author = "Estera P{\'a}ldyov{\'a} and E. Bereczki and M. S{\'a}ntha and T. Wenger and A. Borsodi and S. Benyhe",
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T1 - Altered gene expression and functional activity of opioid receptors in the cerebellum of CB1 cannabinoid receptor knockout mice after acute treatments with cannabinoids

AU - Páldyová, Estera

AU - Bereczki, E.

AU - Sántha, M.

AU - Wenger, T.

AU - Borsodi, A.

AU - Benyhe, S.

PY - 2007/11

Y1 - 2007/11

N2 - Numerous studies have shown functional links between the cannabinoid and opioid systems. The goal of this study was to evaluate whether acute treatments by endogenous cannabinoid agonist, selective CB1 or CB2 receptor antagonists modulate the expression of μ-(MOR) and δ-(DOR) opioid receptor mRNA levels and functional activity in the cerebellum of transgenic mice deficient in the CB1 type of cannabis receptors. We examined the effect of noladin ether (endogenous cannabinoid agonist) pretreatment on MOR and DOR mRNA expression by using reverse transcription and real-time polimerase chain reaction (PCR) and the ability of subsequent application of the opioid agonists to activate G-proteins, as measured by [ 35S]GTPγS binding, in wild-type (CB1 +/+) and CB1 cannabinoid receptor deficient (CB1 -/-, 'knockout', K.O.) mice. The acute administration of noladin ether markedly reduced MOR-mediated G-protein activation and caused a significant increase in the level of MOR mRNAs in the cerebella of wild-type, but not in the CB1 -/- mice. No significant differences were observed in DOR functional activity and mRNA expression in wild-type animals. In CB1 -/- mice the expression of DOR mRNA increased after noladin ether treatment, but no changes were found in DOR functional activity. In addition, Rimonabant (selective central cannabinoid CB1 receptor antagonist) and SR144528 (selective peripheral cannabinoid CB2 receptor antagonist) caused significant potentiation in MOR functional activity in the wild-type animals, whereas DOR mediated G-protein activation was increased in the CB1 -/- mice. In contrast, Rimonabant and SR144528 decreased the MOR and DOR mRNA expressions in both CB1 +/+ and CB1 -/- mice. Taken together, these results indicate that acute treatment with cannabinoids causes alterations in MOR and DOR mRNA expression and functional activity in the cerebella of wild-type and CB1 knockout mice indicating indirect interactions between these two signaling systems.

AB - Numerous studies have shown functional links between the cannabinoid and opioid systems. The goal of this study was to evaluate whether acute treatments by endogenous cannabinoid agonist, selective CB1 or CB2 receptor antagonists modulate the expression of μ-(MOR) and δ-(DOR) opioid receptor mRNA levels and functional activity in the cerebellum of transgenic mice deficient in the CB1 type of cannabis receptors. We examined the effect of noladin ether (endogenous cannabinoid agonist) pretreatment on MOR and DOR mRNA expression by using reverse transcription and real-time polimerase chain reaction (PCR) and the ability of subsequent application of the opioid agonists to activate G-proteins, as measured by [ 35S]GTPγS binding, in wild-type (CB1 +/+) and CB1 cannabinoid receptor deficient (CB1 -/-, 'knockout', K.O.) mice. The acute administration of noladin ether markedly reduced MOR-mediated G-protein activation and caused a significant increase in the level of MOR mRNAs in the cerebella of wild-type, but not in the CB1 -/- mice. No significant differences were observed in DOR functional activity and mRNA expression in wild-type animals. In CB1 -/- mice the expression of DOR mRNA increased after noladin ether treatment, but no changes were found in DOR functional activity. In addition, Rimonabant (selective central cannabinoid CB1 receptor antagonist) and SR144528 (selective peripheral cannabinoid CB2 receptor antagonist) caused significant potentiation in MOR functional activity in the wild-type animals, whereas DOR mediated G-protein activation was increased in the CB1 -/- mice. In contrast, Rimonabant and SR144528 decreased the MOR and DOR mRNA expressions in both CB1 +/+ and CB1 -/- mice. Taken together, these results indicate that acute treatment with cannabinoids causes alterations in MOR and DOR mRNA expression and functional activity in the cerebella of wild-type and CB1 knockout mice indicating indirect interactions between these two signaling systems.

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KW - Opioid receptors

KW - Real-time PCR

KW - Rimonabant

KW - SR144528

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U2 - 10.1556/ABiol.58.2007.Suppl.9

DO - 10.1556/ABiol.58.2007.Suppl.9

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JO - Acta Biologica Hungarica

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