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] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| 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] |
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| ISSN: | 00333158 |
| DOI: | 10.1007/s00213-019-05286-0 |
