Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants
dc.creator | Hill, Rebecca D. | |
dc.creator | Shetty, Ritu A. | |
dc.creator | Sumien, Nathalie | |
dc.creator | Forster, Michael J. | |
dc.creator | Gatch, Michael B. | |
dc.creator.orcid | 0000-0003-3474-211X (Gatch, Michael B.) | |
dc.creator.orcid | 0000-0002-0077-9873 (Sumien, Nathalie) | |
dc.creator.orcid | 0000-0003-4240-6423 (Shetty, Ritu A.) | |
dc.date.accessioned | 2023-09-08T21:41:18Z | |
dc.date.available | 2023-09-08T21:41:18Z | |
dc.date.issued | 2023-08-21 | |
dc.description.abstract | AIMS: Benzofurans are used recreationally, due their ability to cause psychostimulant and/or entactogenic effects, but unfortunately produce substantial adverse effects, including death. Three benzofurans 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-APDB), 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-MAPB) and 6-(2-aminopropyl) benzofuran (6-APB) were tested to determine their behavioral effects in comparison with 2,3-methylenedioxymethamphetamine (MDMA), cocaine, and methamphetamine. METHODS: Locomotor activity was tested in groups of 8 male Swiss-Webster mice in an open-field task to screen for locomotor stimulant or depressant effects and to identify behaviorally active doses and times of peak effect. Discriminative stimulus effects were tested in groups of 6 male Sprague-Dawley rats trained to discriminate MDMA (1.5 mg/kg), cocaine (10 mg/kg), or methamphetamine (1 mg/kg) from saline using a FR 10 for food in a two-lever operant task. RESULTS: In the locomotor activity test, MDMA (ED(50) = 8.34 mg/kg) produced peak stimulant effects 60 to 80 min following injection. 5-MAPB (ED(50) = 0.92 mg/kg) produced modest stimulant effects 50 to 80 min after injection, whereas 6-APB (ED(50) = 1.96 mg/kg) produced a robust stimulant effect 20 to 50 min after injection. 5-APDB produced an early depressant phase (ED(50) = 3.38 mg/kg) followed by a modest stimulant phase (ED(50) = 2.57 mg/kg) 20 to 50 min after injection. In the drug discrimination tests, 5-APDB (ED(50) = 1.02 mg/kg), 5-MAPB (ED(50) = 1.00 mg/kg) and 6-APB (ED(50) = 0.32 mg/kg) fully substituted in MDMA-trained rats, whereas only 5-MAPB fully substituted for cocaine, and no compounds fully substituted for methamphetamine. CONCLUSIONS: The synthetic benzofuran compound 5-APDB and 5-MAPB produced weak locomotor effects, whereas 6-APB produced robust locomotor stimulant effects. All compounds were more potent than MDMA. All three compounds fully substituted in MDMA-trained rats suggesting similar subjective effects. Taken together, these results suggest that these benzofuran compounds may have abuse liability as substitutes for MDMA. | |
dc.description.sponsorship | Funding Sources: N01DA-18-8936. | |
dc.identifier.citation | Hill, R. D., Shetty, R. A., Sumien, N., Forster, M. J., & Gatch, M. B. (2023). Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants. Drug and alcohol dependence reports, 8, 100182. https://doi.org/10.1016/j.dadr.2023.100182 | |
dc.identifier.issn | 2772-7246 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12503/32402 | |
dc.identifier.volume | 8 | |
dc.publisher | Elsevier B.V. | |
dc.relation.uri | https://doi.org/10.1016/j.dadr.2023.100182 | |
dc.rights.holder | © 2023 The Author(s). | |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | Drug and Alcohol Dependence Reports | |
dc.subject | Cocaine | |
dc.subject | Drug discrimination | |
dc.subject | MDMA | |
dc.subject | Methamphetamine | |
dc.subject | Rats | |
dc.title | Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants | |
dc.type | Article | |
dc.type.material | text |
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