Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants

Date

2023-08-21

Authors

Hill, Rebecca D.
Shetty, Ritu A.
Sumien, Nathalie
Forster, Michael J.
Gatch, Michael B.

ORCID

0000-0003-3474-211X (Gatch, Michael B.)
0000-0002-0077-9873 (Sumien, Nathalie)
0000-0003-4240-6423 (Shetty, Ritu A.)

Journal Title

Journal ISSN

Volume Title

Publisher

Elsevier B.V.

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.

Description

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

Rights

© 2023 The Author(s).

License

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)