Self-administration of benzodiazepine and cocaine combinations by male and female rhesus monkeys in a choice procedure: role of α1 subunit–containing GABAA receptors.
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| Title: | Self-administration of benzodiazepine and cocaine combinations by male and female rhesus monkeys in a choice procedure: role of α1 subunit–containing GABA |
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| Authors: | Huskinson, Sally L. (AUTHOR), Freeman, K. B. (AUTHOR), Rowlett, J. K. (AUTHOR) |
| Source: | Psychopharmacology. Nov2019, Vol. 236 Issue 11, p3271-3279. 9p. 3 Graphs. |
| Subjects: | Cocaine, Rhesus monkeys, GABA receptors, Benzodiazepines, Drug abuse |
| Abstract: | Rationale: Compounds lacking efficacy at the α1 subunit–containing GABAA (α1GABAA) receptor appear to have reduced abuse potential compared with those having measurable efficacy at this receptor, though their self-administration in nonhuman primates is dependent upon past drug experience. Objectives: We used a drug vs. drug choice procedure to evaluate the hypothesis that L-838,417, a compound lacking efficacy at αGABAA receptors, would not enhance cocaine choice in monkeys trained to self-administer cocaine. We also hypothesized that zolpidem, a compound with preferential modulation of ⍺1GABAA receptors and midazolam, a nonselective benzodiazepine, would enhance cocaine choice in this procedure. Methods: One female and three male rhesus monkeys chose between cocaine alone (0.1 mg/kg/injection) vs. the same dose of cocaine combined with midazolam (0.003–0.1 mg/kg/injection), zolpidem (0.003–0.3 mg/kg/injection), or L-838-417 (0.01–0.1 mg/kg/injection). In addition, we evaluated choice between saline and L-838,417 at select doses to determine whether L-838,417 would function as a reinforcer on its own. Results: Consistent with our hypotheses, midazolam- and zolpidem-cocaine mixtures were chosen over cocaine alone at sufficiently high doses. However, L-838,417-cocaine mixtures also were chosen over cocaine alone in three of four subjects with at least one dose. When available alone vs. saline, L-838,417 did not function as a reinforcer in any subject. Conclusion: Compounds that lack efficacy at α1GABAA receptors may have low abuse potential compared to classic benzodiazepines, but self-administration of these compounds is context-dependent. [ABSTRACT FROM AUTHOR] |
| Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 139478885 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Self-administration of benzodiazepine and cocaine combinations by male and female rhesus monkeys in a choice procedure: role of α1 subunit–containing GABA<subscript>A</subscript> receptors. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Huskinson%2C+Sally+L%2E%22">Huskinson, Sally L.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Freeman%2C+K%2E+B%2E%22">Freeman, K. B.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rowlett%2C+J%2E+K%2E%22">Rowlett, J. K.</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Nov2019, Vol. 236 Issue 11, p3271-3279. 9p. 3 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Cocaine%22">Cocaine</searchLink><br /><searchLink fieldCode="DE" term="%22Rhesus+monkeys%22">Rhesus monkeys</searchLink><br /><searchLink fieldCode="DE" term="%22GABA+receptors%22">GABA receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Benzodiazepines%22">Benzodiazepines</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+abuse%22">Drug abuse</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Rationale: Compounds lacking efficacy at the α1 subunit–containing GABAA (α1GABAA) receptor appear to have reduced abuse potential compared with those having measurable efficacy at this receptor, though their self-administration in nonhuman primates is dependent upon past drug experience. Objectives: We used a drug vs. drug choice procedure to evaluate the hypothesis that L-838,417, a compound lacking efficacy at αGABAA receptors, would not enhance cocaine choice in monkeys trained to self-administer cocaine. We also hypothesized that zolpidem, a compound with preferential modulation of ⍺1GABAA receptors and midazolam, a nonselective benzodiazepine, would enhance cocaine choice in this procedure. Methods: One female and three male rhesus monkeys chose between cocaine alone (0.1 mg/kg/injection) vs. the same dose of cocaine combined with midazolam (0.003–0.1 mg/kg/injection), zolpidem (0.003–0.3 mg/kg/injection), or L-838-417 (0.01–0.1 mg/kg/injection). In addition, we evaluated choice between saline and L-838,417 at select doses to determine whether L-838,417 would function as a reinforcer on its own. Results: Consistent with our hypotheses, midazolam- and zolpidem-cocaine mixtures were chosen over cocaine alone at sufficiently high doses. However, L-838,417-cocaine mixtures also were chosen over cocaine alone in three of four subjects with at least one dose. When available alone vs. saline, L-838,417 did not function as a reinforcer in any subject. Conclusion: Compounds that lack efficacy at α1GABAA receptors may have low abuse potential compared to classic benzodiazepines, but self-administration of these compounds is context-dependent. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1007/s00213-019-05286-0 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 9 StartPage: 3271 Subjects: – SubjectFull: Cocaine Type: general – SubjectFull: Rhesus monkeys Type: general – SubjectFull: GABA receptors Type: general – SubjectFull: Benzodiazepines Type: general – SubjectFull: Drug abuse Type: general Titles: – TitleFull: Self-administration of benzodiazepine and cocaine combinations by male and female rhesus monkeys in a choice procedure: role of α1 subunit–containing GABAA receptors. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Huskinson, Sally L. – PersonEntity: Name: NameFull: Freeman, K. B. – PersonEntity: Name: NameFull: Rowlett, J. K. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 11 Text: Nov2019 Type: published Y: 2019 Identifiers: – Type: issn-print Value: 00333158 Numbering: – Type: volume Value: 236 – Type: issue Value: 11 Titles: – TitleFull: Psychopharmacology Type: main |
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