Evaluation of the reinforcing and discriminative stimulus effects of 1,4-butanediol and gamma-butyrolactone in rhesus monkeys.
Identifieur interne : 001D96 ( Main/Corpus ); précédent : 001D95; suivant : 001D97Evaluation of the reinforcing and discriminative stimulus effects of 1,4-butanediol and gamma-butyrolactone in rhesus monkeys.
Auteurs : Lance R. Mcmahon ; Andrew Coop ; Charles P. France ; Gail Winger ; William L. WoolvertonSource :
- European journal of pharmacology [ 0014-2999 ] ; 2003.
English descriptors
- KwdEn :
- 4-Butyrolactone (administration & dosage), 4-Butyrolactone (pharmacology), Animals (MeSH), Butylene Glycols (administration & dosage), Butylene Glycols (pharmacology), Discrimination Learning (drug effects), Flumazenil (pharmacology), GABA Modulators (pharmacology), Injections, Intravenous (MeSH), Macaca mulatta (MeSH), Male (MeSH), Midazolam (pharmacology), Pentobarbital (pharmacology), Receptors, GABA-A (drug effects), Reinforcement, Psychology (MeSH), Self Administration (MeSH).
- MESH :
- chemical , administration & dosage : 4-Butyrolactone, Butylene Glycols.
- chemical , drug effects : Receptors, GABA-A.
- chemical , pharmacology : 4-Butyrolactone, Butylene Glycols, Flumazenil, GABA Modulators, Midazolam, Pentobarbital.
- drug effects : Discrimination Learning.
- Animals, Injections, Intravenous, Macaca mulatta, Male, Reinforcement, Psychology, Self Administration.
Abstract
Metabolic precursors and prodrugs of gamma-hydroxybutyrate (GHB), including 1,4-butanediol (BDL) and gamma-butyrolactone (GBL), have sedative and anesthetic effects and might have positive reinforcing effects. BDL and GBL were evaluated using behavioral procedures that measure positive reinforcing effects and discriminative stimulus effects of drugs that modulate gamma-aminobutyric acid (GABA) at the GABA(A) receptor complex. One group of rhesus monkeys could respond for saline or the barbiturate methohexital (i.v.) in a self-administration paradigm. Two other groups of monkeys discriminated the barbiturate pentobarbital (i.g.) or the benzodiazepine midazolam (s.c.) from saline in a drug discrimination paradigm; another group of monkeys was treated with the benzodiazepine diazepam (5.6 mg/kg/day, p.o.) and discriminated the benzodiazepine antagonist flumazenil (s.c.) from vehicle. In self-administration experiments, methohexital and not BDL (0.1-3.2 mg/kg/injection) or GBL (0.1-3.2 mg/kg/injection) reliably maintained responding above saline levels. BDL and GBL, up to doses that suppressed responding, did not substitute for pentobarbital, midazolam or flumazenil. The onset of action for both drugs to decrease response rate was delayed (90 min for GBL and 150 min for BDL). These results suggest that any abuse-related effects of BDL and GBL are qualitatively different from the abuse-related effects of GABA(A) receptor modulators and further indicate that BDL and GBL do not have positive reinforcing effects in rhesus monkeys experienced with self-administration of a short-acting sedative-hypnotic.
DOI: 10.1016/s0014-2999(03)01486-9
PubMed: 12679147
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Evaluation of the reinforcing and discriminative stimulus effects of 1,4-butanediol and gamma-butyrolactone in rhesus monkeys.</title><author><name sortKey="Mcmahon, Lance R" sort="Mcmahon, Lance R" uniqKey="Mcmahon L" first="Lance R" last="Mcmahon">Lance R. Mcmahon</name><affiliation><nlm:affiliation>Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Coop, Andrew" sort="Coop, Andrew" uniqKey="Coop A" first="Andrew" last="Coop">Andrew Coop</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><author><name sortKey="Winger, Gail" sort="Winger, Gail" uniqKey="Winger G" first="Gail" last="Winger">Gail Winger</name></author><author><name sortKey="Woolverton, William L" sort="Woolverton, William L" uniqKey="Woolverton W" first="William L" last="Woolverton">William L. Woolverton</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2003">2003</date><idno type="RBID">pubmed:12679147</idno><idno type="pmid">12679147</idno><idno type="doi">10.1016/s0014-2999(03)01486-9</idno><idno type="wicri:Area/Main/Corpus">001D96</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001D96</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Evaluation of the reinforcing and discriminative stimulus effects of 1,4-butanediol and gamma-butyrolactone in rhesus monkeys.</title><author><name sortKey="Mcmahon, Lance R" sort="Mcmahon, Lance R" uniqKey="Mcmahon L" first="Lance R" last="Mcmahon">Lance R. Mcmahon</name><affiliation><nlm:affiliation>Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Coop, Andrew" sort="Coop, Andrew" uniqKey="Coop A" first="Andrew" last="Coop">Andrew Coop</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><author><name sortKey="Winger, Gail" sort="Winger, Gail" uniqKey="Winger G" first="Gail" last="Winger">Gail Winger</name></author><author><name sortKey="Woolverton, William L" sort="Woolverton, William L" uniqKey="Woolverton W" first="William L" last="Woolverton">William L. Woolverton</name></author></analytic><series><title level="j">European journal of pharmacology</title><idno type="ISSN">0014-2999</idno><imprint><date when="2003" type="published">2003</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>4-Butyrolactone (administration & dosage)</term><term>4-Butyrolactone (pharmacology)</term><term>Animals (MeSH)</term><term>Butylene Glycols (administration & dosage)</term><term>Butylene Glycols (pharmacology)</term><term>Discrimination Learning (drug effects)</term><term>Flumazenil (pharmacology)</term><term>GABA Modulators (pharmacology)</term><term>Injections, Intravenous (MeSH)</term><term>Macaca mulatta (MeSH)</term><term>Male (MeSH)</term><term>Midazolam (pharmacology)</term><term>Pentobarbital (pharmacology)</term><term>Receptors, GABA-A (drug effects)</term><term>Reinforcement, Psychology (MeSH)</term><term>Self Administration (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>4-Butyrolactone</term><term>Butylene Glycols</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, GABA-A</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>4-Butyrolactone</term><term>Butylene Glycols</term><term>Flumazenil</term><term>GABA Modulators</term><term>Midazolam</term><term>Pentobarbital</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Discrimination Learning</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Injections, Intravenous</term><term>Macaca mulatta</term><term>Male</term><term>Reinforcement, Psychology</term><term>Self Administration</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Metabolic precursors and prodrugs of gamma-hydroxybutyrate (GHB), including 1,4-butanediol (BDL) and gamma-butyrolactone (GBL), have sedative and anesthetic effects and might have positive reinforcing effects. BDL and GBL were evaluated using behavioral procedures that measure positive reinforcing effects and discriminative stimulus effects of drugs that modulate gamma-aminobutyric acid (GABA) at the GABA(A) receptor complex. One group of rhesus monkeys could respond for saline or the barbiturate methohexital (i.v.) in a self-administration paradigm. Two other groups of monkeys discriminated the barbiturate pentobarbital (i.g.) or the benzodiazepine midazolam (s.c.) from saline in a drug discrimination paradigm; another group of monkeys was treated with the benzodiazepine diazepam (5.6 mg/kg/day, p.o.) and discriminated the benzodiazepine antagonist flumazenil (s.c.) from vehicle. In self-administration experiments, methohexital and not BDL (0.1-3.2 mg/kg/injection) or GBL (0.1-3.2 mg/kg/injection) reliably maintained responding above saline levels. BDL and GBL, up to doses that suppressed responding, did not substitute for pentobarbital, midazolam or flumazenil. The onset of action for both drugs to decrease response rate was delayed (90 min for GBL and 150 min for BDL). These results suggest that any abuse-related effects of BDL and GBL are qualitatively different from the abuse-related effects of GABA(A) receptor modulators and further indicate that BDL and GBL do not have positive reinforcing effects in rhesus monkeys experienced with self-administration of a short-acting sedative-hypnotic.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">12679147</PMID><DateCompleted><Year>2004</Year><Month>03</Month><Day>08</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>10</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0014-2999</ISSN><JournalIssue CitedMedium="Print"><Volume>466</Volume><Issue>1-2</Issue><PubDate><Year>2003</Year><Month>Apr</Month><Day>11</Day></PubDate></JournalIssue><Title>European journal of pharmacology</Title><ISOAbbreviation>Eur J Pharmacol</ISOAbbreviation></Journal><ArticleTitle>Evaluation of the reinforcing and discriminative stimulus effects of 1,4-butanediol and gamma-butyrolactone in rhesus monkeys.</ArticleTitle><Pagination><MedlinePgn>113-20</MedlinePgn></Pagination><Abstract><AbstractText>Metabolic precursors and prodrugs of gamma-hydroxybutyrate (GHB), including 1,4-butanediol (BDL) and gamma-butyrolactone (GBL), have sedative and anesthetic effects and might have positive reinforcing effects. BDL and GBL were evaluated using behavioral procedures that measure positive reinforcing effects and discriminative stimulus effects of drugs that modulate gamma-aminobutyric acid (GABA) at the GABA(A) receptor complex. One group of rhesus monkeys could respond for saline or the barbiturate methohexital (i.v.) in a self-administration paradigm. Two other groups of monkeys discriminated the barbiturate pentobarbital (i.g.) or the benzodiazepine midazolam (s.c.) from saline in a drug discrimination paradigm; another group of monkeys was treated with the benzodiazepine diazepam (5.6 mg/kg/day, p.o.) and discriminated the benzodiazepine antagonist flumazenil (s.c.) from vehicle. In self-administration experiments, methohexital and not BDL (0.1-3.2 mg/kg/injection) or GBL (0.1-3.2 mg/kg/injection) reliably maintained responding above saline levels. BDL and GBL, up to doses that suppressed responding, did not substitute for pentobarbital, midazolam or flumazenil. The onset of action for both drugs to decrease response rate was delayed (90 min for GBL and 150 min for BDL). These results suggest that any abuse-related effects of BDL and GBL are qualitatively different from the abuse-related effects of GABA(A) receptor modulators and further indicate that BDL and GBL do not have positive reinforcing effects in rhesus monkeys experienced with self-administration of a short-acting sedative-hypnotic.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>McMahon</LastName><ForeName>Lance R</ForeName><Initials>LR</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coop</LastName><ForeName>Andrew</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>France</LastName><ForeName>Charles P</ForeName><Initials>CP</Initials></Author><Author ValidYN="Y"><LastName>Winger</LastName><ForeName>Gail</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Woolverton</LastName><ForeName>William L</ForeName><Initials>WL</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>DA00211</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>DA09139</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>DA09157</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>DA09163</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>DA15343</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Eur J Pharmacol</MedlineTA><NlmUniqueID>1254354</NlmUniqueID><ISSNLinking>0014-2999</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002072">Butylene Glycols</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018757">GABA Modulators</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011963">Receptors, GABA-A</NameOfSubstance></Chemical><Chemical><RegistryNumber>40P7XK9392</RegistryNumber><NameOfSubstance UI="D005442">Flumazenil</NameOfSubstance></Chemical><Chemical><RegistryNumber>7XOO2LE6G3</RegistryNumber><NameOfSubstance UI="C039681">1,4-butanediol</NameOfSubstance></Chemical><Chemical><RegistryNumber>I4744080IR</RegistryNumber><NameOfSubstance UI="D010424">Pentobarbital</NameOfSubstance></Chemical><Chemical><RegistryNumber>OL659KIY4X</RegistryNumber><NameOfSubstance UI="D015107">4-Butyrolactone</NameOfSubstance></Chemical><Chemical><RegistryNumber>R60L0SM5BC</RegistryNumber><NameOfSubstance UI="D008874">Midazolam</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D015107" MajorTopicYN="N">4-Butyrolactone</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002072" MajorTopicYN="N">Butylene Glycols</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004193" MajorTopicYN="N">Discrimination Learning</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005442" MajorTopicYN="N">Flumazenil</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018757" MajorTopicYN="N">GABA Modulators</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007275" MajorTopicYN="N">Injections, Intravenous</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008253" MajorTopicYN="N">Macaca mulatta</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008874" MajorTopicYN="N">Midazolam</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010424" MajorTopicYN="N">Pentobarbital</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011963" MajorTopicYN="N">Receptors, GABA-A</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012054" MajorTopicYN="Y">Reinforcement, Psychology</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012646" MajorTopicYN="N">Self Administration</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate 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