Interactions between μ-opioid receptor agonists and cannabinoid receptor agonists in rhesus monkeys: antinociception, drug discrimination, and drug self-administration.
Identifieur interne : 001427 ( Main/Corpus ); précédent : 001426; suivant : 001428Interactions between μ-opioid receptor agonists and cannabinoid receptor agonists in rhesus monkeys: antinociception, drug discrimination, and drug self-administration.
Auteurs : David R. Maguire ; Wenjuan Yang ; Charles P. FranceSource :
- The Journal of pharmacology and experimental therapeutics [ 1521-0103 ] ; 2013.
English descriptors
- KwdEn :
- Analgesics (pharmacology), Analgesics, Opioid (pharmacology), Animals (MeSH), Benzoxazines (pharmacology), Cannabinoid Receptor Agonists (pharmacology), Cyclohexanols (pharmacology), Data Interpretation, Statistical (MeSH), Discrimination, Psychological (drug effects), Dose-Response Relationship, Drug (MeSH), Dronabinol (pharmacology), Heroin Dependence (psychology), Hot Temperature (MeSH), Macaca mulatta (MeSH), Morphine (pharmacology), Morpholines (pharmacology), Naphthalenes (pharmacology), Pain Measurement (drug effects), Receptors, Cannabinoid (drug effects), Receptors, Opioid, mu (agonists), Self Administration (MeSH).
- MESH :
- chemical , agonists : Receptors, Opioid, mu.
- chemical , drug effects : Receptors, Cannabinoid.
- chemical , pharmacology : Analgesics, Analgesics, Opioid, Benzoxazines, Cannabinoid Receptor Agonists, Cyclohexanols, Dronabinol, Morphine, Morpholines, Naphthalenes.
- drug effects : Discrimination, Psychological, Pain Measurement.
- psychology : Heroin Dependence.
- Animals, Data Interpretation, Statistical, Dose-Response Relationship, Drug, Hot Temperature, Macaca mulatta, Self Administration.
Abstract
Cannabinoid receptor agonists enhance the antinociceptive effects of μ-opioid receptor agonists, which suggests that combinations of these drugs might enhance therapeutic effectiveness (e.g., analgesia). However, it is not clear whether combinations of these drugs also enhance abuse or dependence liability. This experiment examined whether combinations of cannabinoids and opioids that enhance antinociception also increase abuse-related effects by studying the effects of the cannabinoid receptor agonists 2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol (CP 55,940) and (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212) on the antinociceptive, discriminative stimulus, and positive reinforcing effects of μ-opioid receptor agonists in rhesus monkeys. In one group of monkeys (n = 3), morphine (0.1-5.6 mg/kg s.c.), CP 55,940 (0.0032-0.032 mg/kg s.c.), and WIN 55,212 (0.1-1.0 mg/kg s.c.) dose-dependently increased tail withdrawal latency from 50°C water, and pretreatment with small, otherwise ineffective, doses of CP 55,940 and WIN 55,212 shifted the morphine dose-effect curve to the left. In monkeys (n = 3) discriminating 3.2 mg/kg morphine, CP 55,940 (0.01-0.032 mg/kg s.c.) and WIN 55,212 (0.1-1.78 mg/kg s.c.) attenuated the discriminative stimulus effects of morphine, shifting the dose-effect curve to the right. In monkeys (n = 4) self-administering heroin (0.32-32.0 µg/kg/infusion i.v.), CP 55,940 (0.001-0.032 mg/kg s.c.), and WIN 55,212 (0.1-1.0 mg/kg s.c.) shifted the heroin dose-effect curve rightward and downward. Cannabinoid receptor agonists CP 55,940 and WIN 55,212 enhanced the antinociceptive effects but not the discriminative stimulus or positive reinforcing effects of μ-opioid receptor agonists in rhesus monkeys, supporting the view that combining cannabinoid and opioid receptor agonists might result in enhanced treatment effectiveness for pain without similarly enhancing abuse and dependence liability.
DOI: 10.1124/jpet.113.204099
PubMed: 23536317
PubMed Central: PMC3657106
Links to Exploration step
pubmed:23536317Le document en format XML
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Maguire</name><affiliation><nlm:affiliation>Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Yang, Wenjuan" sort="Yang, Wenjuan" uniqKey="Yang W" first="Wenjuan" last="Yang">Wenjuan Yang</name></author><author><name sortKey="France, Charles P" sort="France, Charles P" uniqKey="France C" first="Charles P" last="France">Charles P. France</name></author></analytic><series><title level="j">The Journal of pharmacology and experimental therapeutics</title><idno type="eISSN">1521-0103</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Analgesics (pharmacology)</term><term>Analgesics, Opioid (pharmacology)</term><term>Animals (MeSH)</term><term>Benzoxazines (pharmacology)</term><term>Cannabinoid Receptor Agonists (pharmacology)</term><term>Cyclohexanols (pharmacology)</term><term>Data Interpretation, Statistical (MeSH)</term><term>Discrimination, Psychological (drug effects)</term><term>Dose-Response Relationship, Drug (MeSH)</term><term>Dronabinol (pharmacology)</term><term>Heroin Dependence (psychology)</term><term>Hot Temperature (MeSH)</term><term>Macaca mulatta (MeSH)</term><term>Morphine (pharmacology)</term><term>Morpholines (pharmacology)</term><term>Naphthalenes (pharmacology)</term><term>Pain Measurement (drug effects)</term><term>Receptors, Cannabinoid (drug effects)</term><term>Receptors, Opioid, mu (agonists)</term><term>Self Administration (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="agonists" xml:lang="en"><term>Receptors, Opioid, mu</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Cannabinoid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Analgesics</term><term>Analgesics, Opioid</term><term>Benzoxazines</term><term>Cannabinoid Receptor Agonists</term><term>Cyclohexanols</term><term>Dronabinol</term><term>Morphine</term><term>Morpholines</term><term>Naphthalenes</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Discrimination, Psychological</term><term>Pain Measurement</term></keywords><keywords scheme="MESH" qualifier="psychology" xml:lang="en"><term>Heroin Dependence</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Data Interpretation, Statistical</term><term>Dose-Response Relationship, Drug</term><term>Hot Temperature</term><term>Macaca mulatta</term><term>Self Administration</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cannabinoid receptor agonists enhance the antinociceptive effects of μ-opioid receptor agonists, which suggests that combinations of these drugs might enhance therapeutic effectiveness (e.g., analgesia). However, it is not clear whether combinations of these drugs also enhance abuse or dependence liability. This experiment examined whether combinations of cannabinoids and opioids that enhance antinociception also increase abuse-related effects by studying the effects of the cannabinoid receptor agonists 2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol (CP 55,940) and (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212) on the antinociceptive, discriminative stimulus, and positive reinforcing effects of μ-opioid receptor agonists in rhesus monkeys. In one group of monkeys (n = 3), morphine (0.1-5.6 mg/kg s.c.), CP 55,940 (0.0032-0.032 mg/kg s.c.), and WIN 55,212 (0.1-1.0 mg/kg s.c.) dose-dependently increased tail withdrawal latency from 50°C water, and pretreatment with small, otherwise ineffective, doses of CP 55,940 and WIN 55,212 shifted the morphine dose-effect curve to the left. In monkeys (n = 3) discriminating 3.2 mg/kg morphine, CP 55,940 (0.01-0.032 mg/kg s.c.) and WIN 55,212 (0.1-1.78 mg/kg s.c.) attenuated the discriminative stimulus effects of morphine, shifting the dose-effect curve to the right. In monkeys (n = 4) self-administering heroin (0.32-32.0 µg/kg/infusion i.v.), CP 55,940 (0.001-0.032 mg/kg s.c.), and WIN 55,212 (0.1-1.0 mg/kg s.c.) shifted the heroin dose-effect curve rightward and downward. Cannabinoid receptor agonists CP 55,940 and WIN 55,212 enhanced the antinociceptive effects but not the discriminative stimulus or positive reinforcing effects of μ-opioid receptor agonists in rhesus monkeys, supporting the view that combining cannabinoid and opioid receptor agonists might result in enhanced treatment effectiveness for pain without similarly enhancing abuse and dependence liability.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23536317</PMID><DateCompleted><Year>2013</Year><Month>07</Month><Day>16</Day></DateCompleted><DateRevised><Year>2021</Year><Month>02</Month><Day>23</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1521-0103</ISSN><JournalIssue CitedMedium="Internet"><Volume>345</Volume><Issue>3</Issue><PubDate><Year>2013</Year><Month>Jun</Month></PubDate></JournalIssue><Title>The Journal of pharmacology and experimental therapeutics</Title><ISOAbbreviation>J Pharmacol Exp Ther</ISOAbbreviation></Journal><ArticleTitle>Interactions between μ-opioid receptor agonists and cannabinoid receptor agonists in rhesus monkeys: antinociception, drug discrimination, and drug self-administration.</ArticleTitle><Pagination><MedlinePgn>354-62</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1124/jpet.113.204099</ELocationID><Abstract><AbstractText>Cannabinoid receptor agonists enhance the antinociceptive effects of μ-opioid receptor agonists, which suggests that combinations of these drugs might enhance therapeutic effectiveness (e.g., analgesia). However, it is not clear whether combinations of these drugs also enhance abuse or dependence liability. This experiment examined whether combinations of cannabinoids and opioids that enhance antinociception also increase abuse-related effects by studying the effects of the cannabinoid receptor agonists 2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol (CP 55,940) and (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212) on the antinociceptive, discriminative stimulus, and positive reinforcing effects of μ-opioid receptor agonists in rhesus monkeys. In one group of monkeys (n = 3), morphine (0.1-5.6 mg/kg s.c.), CP 55,940 (0.0032-0.032 mg/kg s.c.), and WIN 55,212 (0.1-1.0 mg/kg s.c.) dose-dependently increased tail withdrawal latency from 50°C water, and pretreatment with small, otherwise ineffective, doses of CP 55,940 and WIN 55,212 shifted the morphine dose-effect curve to the left. In monkeys (n = 3) discriminating 3.2 mg/kg morphine, CP 55,940 (0.01-0.032 mg/kg s.c.) and WIN 55,212 (0.1-1.78 mg/kg s.c.) attenuated the discriminative stimulus effects of morphine, shifting the dose-effect curve to the right. In monkeys (n = 4) self-administering heroin (0.32-32.0 µg/kg/infusion i.v.), CP 55,940 (0.001-0.032 mg/kg s.c.), and WIN 55,212 (0.1-1.0 mg/kg s.c.) shifted the heroin dose-effect curve rightward and downward. Cannabinoid receptor agonists CP 55,940 and WIN 55,212 enhanced the antinociceptive effects but not the discriminative stimulus or positive reinforcing effects of μ-opioid receptor agonists in rhesus monkeys, supporting the view that combining cannabinoid and opioid receptor agonists might result in enhanced treatment effectiveness for pain without similarly enhancing abuse and dependence liability.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Maguire</LastName><ForeName>David R</ForeName><Initials>DR</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Wenjuan</ForeName><Initials>W</Initials></Author><Author ValidYN="Y"><LastName>France</LastName><ForeName>Charles P</ForeName><Initials>CP</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>K05DA17918</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32DA031115</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K05 DA017918</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 DA005018</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 DA031115</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01DA005018</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType 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MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D048588" MajorTopicYN="N">Benzoxazines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D063386" MajorTopicYN="N">Cannabinoid Receptor Agonists</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003511" MajorTopicYN="N">Cyclohexanols</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003627" MajorTopicYN="N">Data Interpretation, Statistical</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004192" MajorTopicYN="N">Discrimination, Psychological</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013759" MajorTopicYN="N">Dronabinol</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006556" MajorTopicYN="N">Heroin Dependence</DescriptorName><QualifierName UI="Q000523" MajorTopicYN="N">psychology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006358" MajorTopicYN="N">Hot Temperature</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008253" MajorTopicYN="N">Macaca mulatta</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009020" MajorTopicYN="N">Morphine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009025" MajorTopicYN="N">Morpholines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009281" MajorTopicYN="N">Naphthalenes</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010147" MajorTopicYN="N">Pain Measurement</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D043882" MajorTopicYN="N">Receptors, Cannabinoid</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017450" MajorTopicYN="N">Receptors, Opioid, mu</DescriptorName><QualifierName UI="Q000819" MajorTopicYN="Y">agonists</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012646" MajorTopicYN="Y">Self Administration</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>3</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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