Inhibition of morphine tolerance and dependence by diazepam and its relation to μ-opioid receptors in the rat brain and spinal cord
We have recently observed that concomitant administration of diazepam to morphine pellet implanted rats results in the inhibition of the development of morphine tolerance and dependence. We have now analyzed μ-opioid receptors in rats treated with morphine and diazepam for 5 days by using [ 3 H] -DA...
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| Veröffentlicht in: | Brain research 1998-06, Vol.797 (2), p.305-312 |
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| creator | Tejwani, Gopi A Sheu, Ming-Jyh Sribanditmongkol, Pongruk Satyapriya, Ajay |
| description | We have recently observed that concomitant administration of diazepam to morphine pellet implanted rats results in the inhibition of the development of morphine tolerance and dependence. We have now analyzed
μ-opioid receptors in rats treated with morphine and diazepam for 5 days by using
[
3
H]
-DAMGO for binding studies. Male Sprague–Dawley rats were made tolerant and dependent by subcutaneous (s.c.) implantation of six morphine pellets (two pellets on the first day, and four on the second day). Diazepam (0.25 mg/kg b.wt) was injected once daily intraperitoneally (i.p.) for 5 days. Control rats were implanted with placebo pellets and injected once daily with saline or diazepam (i.p.). Animals were administered s.c. naloxone (10 mg/kg) to induce naloxone-precipitated withdrawal syndrome on the final day of the experiment (day 5). There was an up-regulation of
μ-receptor (
B
max increased) in the spinal cord of morphine tolerant (+139%) and dependent (+155%) rats compared to saline treated animals. Diazepam treatment abolished the up-regulation of
μ-receptors in spinal cord of morphine treated rats. In the cortex,
B
max was not affected in morphine tolerant or dependent rats but it decreased by 38% in morphine tolerant and 65% in morphine dependent rats treated with diazepam. The
K
d of
μ-receptors increased in the cortex, striatum and hypothalamus of morphine dependent rats. Diazepam treatment decreased the
K
d of
μ-receptors in the cortex of morphine tolerant and hypothalamus of morphine-dependent rats. These results suggest that diazepam treatment antagonizes the up-regulation of CNS
μ-receptors observed in morphine tolerant rats. In addition, morphine tolerance and dependence may be associated with conversion of
μ-opioid receptors to
μ*-constitutive opioid receptors that are less active, and this conversion is prevented in the brain of animals treated with diazepam. |
| doi_str_mv | 10.1016/S0006-8993(98)00416-8 |
| format | Article |
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μ-opioid receptors in rats treated with morphine and diazepam for 5 days by using
[
3
H]
-DAMGO for binding studies. Male Sprague–Dawley rats were made tolerant and dependent by subcutaneous (s.c.) implantation of six morphine pellets (two pellets on the first day, and four on the second day). Diazepam (0.25 mg/kg b.wt) was injected once daily intraperitoneally (i.p.) for 5 days. Control rats were implanted with placebo pellets and injected once daily with saline or diazepam (i.p.). Animals were administered s.c. naloxone (10 mg/kg) to induce naloxone-precipitated withdrawal syndrome on the final day of the experiment (day 5). There was an up-regulation of
μ-receptor (
B
max increased) in the spinal cord of morphine tolerant (+139%) and dependent (+155%) rats compared to saline treated animals. Diazepam treatment abolished the up-regulation of
μ-receptors in spinal cord of morphine treated rats. In the cortex,
B
max was not affected in morphine tolerant or dependent rats but it decreased by 38% in morphine tolerant and 65% in morphine dependent rats treated with diazepam. The
K
d of
μ-receptors increased in the cortex, striatum and hypothalamus of morphine dependent rats. Diazepam treatment decreased the
K
d of
μ-receptors in the cortex of morphine tolerant and hypothalamus of morphine-dependent rats. These results suggest that diazepam treatment antagonizes the up-regulation of CNS
μ-receptors observed in morphine tolerant rats. In addition, morphine tolerance and dependence may be associated with conversion of
μ-opioid receptors to
μ*-constitutive opioid receptors that are less active, and this conversion is prevented in the brain of animals treated with diazepam.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/S0006-8993(98)00416-8</identifier><identifier>PMID: 9666154</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>London: Elsevier B.V</publisher><subject>Analgesics ; Analgesics, Opioid - pharmacology ; Animals ; Benzodiazepine ; Binding, Competitive - physiology ; Biological and medical sciences ; Brain Chemistry - drug effects ; Brain region ; Central Nervous System - chemistry ; Central Nervous System - drug effects ; CNS ; Constitutive receptor ; Diazepam ; Diazepam - pharmacology ; Drug Interactions ; Drug Tolerance ; Enkephalin, Ala-MePhe-Gly ; Enkephalins - pharmacology ; Hypnotics and Sedatives - pharmacology ; Male ; Medical sciences ; Morphine ; Morphine - pharmacology ; Naloxone - pharmacology ; Narcotic Antagonists - pharmacology ; Neuropharmacology ; Nociceptors - drug effects ; Opioid ; Peripheral tissue ; Pharmacology. Drug treatments ; Radioligand Assay ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu - physiology ; Spinal cord ; Substance Withdrawal Syndrome - drug therapy ; Tolerance ; Tritium ; μ-Opioid receptor</subject><ispartof>Brain research, 1998-06, Vol.797 (2), p.305-312</ispartof><rights>1998 Elsevier Science B.V.</rights><rights>1998 INIST-CNRS</rights><rights>Copyright 1998 Elsevier Science B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-d137c8a50d7b6baafad578ba40af33dd2300c8ce0a6c1137a13d9710aea419d73</citedby><cites>FETCH-LOGICAL-c420t-d137c8a50d7b6baafad578ba40af33dd2300c8ce0a6c1137a13d9710aea419d73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-8993(98)00416-8$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2335025$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9666154$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tejwani, Gopi A</creatorcontrib><creatorcontrib>Sheu, Ming-Jyh</creatorcontrib><creatorcontrib>Sribanditmongkol, Pongruk</creatorcontrib><creatorcontrib>Satyapriya, Ajay</creatorcontrib><title>Inhibition of morphine tolerance and dependence by diazepam and its relation to μ-opioid receptors in the rat brain and spinal cord</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>We have recently observed that concomitant administration of diazepam to morphine pellet implanted rats results in the inhibition of the development of morphine tolerance and dependence. We have now analyzed
μ-opioid receptors in rats treated with morphine and diazepam for 5 days by using
[
3
H]
-DAMGO for binding studies. Male Sprague–Dawley rats were made tolerant and dependent by subcutaneous (s.c.) implantation of six morphine pellets (two pellets on the first day, and four on the second day). Diazepam (0.25 mg/kg b.wt) was injected once daily intraperitoneally (i.p.) for 5 days. Control rats were implanted with placebo pellets and injected once daily with saline or diazepam (i.p.). Animals were administered s.c. naloxone (10 mg/kg) to induce naloxone-precipitated withdrawal syndrome on the final day of the experiment (day 5). There was an up-regulation of
μ-receptor (
B
max increased) in the spinal cord of morphine tolerant (+139%) and dependent (+155%) rats compared to saline treated animals. Diazepam treatment abolished the up-regulation of
μ-receptors in spinal cord of morphine treated rats. In the cortex,
B
max was not affected in morphine tolerant or dependent rats but it decreased by 38% in morphine tolerant and 65% in morphine dependent rats treated with diazepam. The
K
d of
μ-receptors increased in the cortex, striatum and hypothalamus of morphine dependent rats. Diazepam treatment decreased the
K
d of
μ-receptors in the cortex of morphine tolerant and hypothalamus of morphine-dependent rats. These results suggest that diazepam treatment antagonizes the up-regulation of CNS
μ-receptors observed in morphine tolerant rats. In addition, morphine tolerance and dependence may be associated with conversion of
μ-opioid receptors to
μ*-constitutive opioid receptors that are less active, and this conversion is prevented in the brain of animals treated with diazepam.</description><subject>Analgesics</subject><subject>Analgesics, Opioid - pharmacology</subject><subject>Animals</subject><subject>Benzodiazepine</subject><subject>Binding, Competitive - physiology</subject><subject>Biological and medical sciences</subject><subject>Brain Chemistry - drug effects</subject><subject>Brain region</subject><subject>Central Nervous System - chemistry</subject><subject>Central Nervous System - drug effects</subject><subject>CNS</subject><subject>Constitutive receptor</subject><subject>Diazepam</subject><subject>Diazepam - pharmacology</subject><subject>Drug Interactions</subject><subject>Drug Tolerance</subject><subject>Enkephalin, Ala-MePhe-Gly</subject><subject>Enkephalins - pharmacology</subject><subject>Hypnotics and Sedatives - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Morphine</subject><subject>Morphine - pharmacology</subject><subject>Naloxone - pharmacology</subject><subject>Narcotic Antagonists - pharmacology</subject><subject>Neuropharmacology</subject><subject>Nociceptors - drug effects</subject><subject>Opioid</subject><subject>Peripheral tissue</subject><subject>Pharmacology. Drug treatments</subject><subject>Radioligand Assay</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Opioid, mu - physiology</subject><subject>Spinal cord</subject><subject>Substance Withdrawal Syndrome - drug therapy</subject><subject>Tolerance</subject><subject>Tritium</subject><subject>μ-Opioid receptor</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1u1DAURi1EVaaFR6jkBUJ0kXIdJ068Qqjip1IlFsDaurFvNEZJHOwMUlnzWH2GPhPOzGi2rKzP37nX1mHsSsCNAKHefQMAVbRay7e6vQaoRE7P2Ea0TVmosoLnbHNCXrCLlH7mKKWGc3aulVKirjbs79209Z1ffJh46PkY4rz1E_ElDBRxssRxctzRTJOjNXYP3Hn8QzOO-8oviUcacL9hCfzpsQizD97lW0vzEmLiPjdb4hEX3kXMaR1Ms59w4DZE95Kd9TgkenU8L9mPTx-_334p7r9-vrv9cF_YqoSlcEI2tsUaXNOpDrFHVzdthxVgL6VzpQSwrSVAZUVmUUinGwFIWAntGnnJ3hz2zjH82lFazOiTpWHAicIuGaEqqHQFGawPoI0hpUi9maMfMT4YAWa1b_b2zarW6Nbs7Zs2z10dH9h1I7nT1FF37l8fe0wWh3417NMJK6Wsoawz9v6AUZbx21M0yfrVvvNZ6mJc8P_5yD_YdqPt</recordid><startdate>19980629</startdate><enddate>19980629</enddate><creator>Tejwani, Gopi A</creator><creator>Sheu, Ming-Jyh</creator><creator>Sribanditmongkol, Pongruk</creator><creator>Satyapriya, Ajay</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>19980629</creationdate><title>Inhibition of morphine tolerance and dependence by diazepam and its relation to μ-opioid receptors in the rat brain and spinal cord</title><author>Tejwani, Gopi A ; Sheu, Ming-Jyh ; Sribanditmongkol, Pongruk ; Satyapriya, Ajay</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-d137c8a50d7b6baafad578ba40af33dd2300c8ce0a6c1137a13d9710aea419d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Analgesics</topic><topic>Analgesics, Opioid - pharmacology</topic><topic>Animals</topic><topic>Benzodiazepine</topic><topic>Binding, Competitive - physiology</topic><topic>Biological and medical sciences</topic><topic>Brain Chemistry - drug effects</topic><topic>Brain region</topic><topic>Central Nervous System - chemistry</topic><topic>Central Nervous System - drug effects</topic><topic>CNS</topic><topic>Constitutive receptor</topic><topic>Diazepam</topic><topic>Diazepam - pharmacology</topic><topic>Drug Interactions</topic><topic>Drug Tolerance</topic><topic>Enkephalin, Ala-MePhe-Gly</topic><topic>Enkephalins - pharmacology</topic><topic>Hypnotics and Sedatives - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Morphine</topic><topic>Morphine - pharmacology</topic><topic>Naloxone - pharmacology</topic><topic>Narcotic Antagonists - pharmacology</topic><topic>Neuropharmacology</topic><topic>Nociceptors - drug effects</topic><topic>Opioid</topic><topic>Peripheral tissue</topic><topic>Pharmacology. Drug treatments</topic><topic>Radioligand Assay</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Opioid, mu - physiology</topic><topic>Spinal cord</topic><topic>Substance Withdrawal Syndrome - drug therapy</topic><topic>Tolerance</topic><topic>Tritium</topic><topic>μ-Opioid receptor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tejwani, Gopi A</creatorcontrib><creatorcontrib>Sheu, Ming-Jyh</creatorcontrib><creatorcontrib>Sribanditmongkol, Pongruk</creatorcontrib><creatorcontrib>Satyapriya, Ajay</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tejwani, Gopi A</au><au>Sheu, Ming-Jyh</au><au>Sribanditmongkol, Pongruk</au><au>Satyapriya, Ajay</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of morphine tolerance and dependence by diazepam and its relation to μ-opioid receptors in the rat brain and spinal cord</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>1998-06-29</date><risdate>1998</risdate><volume>797</volume><issue>2</issue><spage>305</spage><epage>312</epage><pages>305-312</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>We have recently observed that concomitant administration of diazepam to morphine pellet implanted rats results in the inhibition of the development of morphine tolerance and dependence. We have now analyzed
μ-opioid receptors in rats treated with morphine and diazepam for 5 days by using
[
3
H]
-DAMGO for binding studies. Male Sprague–Dawley rats were made tolerant and dependent by subcutaneous (s.c.) implantation of six morphine pellets (two pellets on the first day, and four on the second day). Diazepam (0.25 mg/kg b.wt) was injected once daily intraperitoneally (i.p.) for 5 days. Control rats were implanted with placebo pellets and injected once daily with saline or diazepam (i.p.). Animals were administered s.c. naloxone (10 mg/kg) to induce naloxone-precipitated withdrawal syndrome on the final day of the experiment (day 5). There was an up-regulation of
μ-receptor (
B
max increased) in the spinal cord of morphine tolerant (+139%) and dependent (+155%) rats compared to saline treated animals. Diazepam treatment abolished the up-regulation of
μ-receptors in spinal cord of morphine treated rats. In the cortex,
B
max was not affected in morphine tolerant or dependent rats but it decreased by 38% in morphine tolerant and 65% in morphine dependent rats treated with diazepam. The
K
d of
μ-receptors increased in the cortex, striatum and hypothalamus of morphine dependent rats. Diazepam treatment decreased the
K
d of
μ-receptors in the cortex of morphine tolerant and hypothalamus of morphine-dependent rats. These results suggest that diazepam treatment antagonizes the up-regulation of CNS
μ-receptors observed in morphine tolerant rats. In addition, morphine tolerance and dependence may be associated with conversion of
μ-opioid receptors to
μ*-constitutive opioid receptors that are less active, and this conversion is prevented in the brain of animals treated with diazepam.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>9666154</pmid><doi>10.1016/S0006-8993(98)00416-8</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-8993 |
| ispartof | Brain research, 1998-06, Vol.797 (2), p.305-312 |
| issn | 0006-8993 1872-6240 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_16404940 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Analgesics Analgesics, Opioid - pharmacology Animals Benzodiazepine Binding, Competitive - physiology Biological and medical sciences Brain Chemistry - drug effects Brain region Central Nervous System - chemistry Central Nervous System - drug effects CNS Constitutive receptor Diazepam Diazepam - pharmacology Drug Interactions Drug Tolerance Enkephalin, Ala-MePhe-Gly Enkephalins - pharmacology Hypnotics and Sedatives - pharmacology Male Medical sciences Morphine Morphine - pharmacology Naloxone - pharmacology Narcotic Antagonists - pharmacology Neuropharmacology Nociceptors - drug effects Opioid Peripheral tissue Pharmacology. Drug treatments Radioligand Assay Rats Rats, Sprague-Dawley Receptors, Opioid, mu - physiology Spinal cord Substance Withdrawal Syndrome - drug therapy Tolerance Tritium μ-Opioid receptor |
| title | Inhibition of morphine tolerance and dependence by diazepam and its relation to μ-opioid receptors in the rat brain and spinal cord |
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