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

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

doi:10.1016/j.dadr.2023.100182

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

Drug Alcohol Depend Rep. 2023 Aug 5:8:100182. doi: 10.1016/j.dadr.2023.100182. eCollection 2023 Sep.

Authors

Rebecca D Hill¹, Ritu A Shetty¹, Nathalie Sumien¹, Michael J Forster¹, Michael B Gatch¹

Affiliation

¹ University of North Texas Health Science Center, Department of Pharmacology and Neuroscience, 3500 Camp Bowie Blvd, Fort Worth, TX 76109, United States.

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 (ED₅₀ = 8.34 mg/kg) produced peak stimulant effects 60 to 80 min following injection. 5-MAPB (ED₅₀ = 0.92 mg/kg) produced modest stimulant effects 50 to 80 min after injection, whereas 6-APB (ED₅₀ = 1.96 mg/kg) produced a robust stimulant effect 20 to 50 min after injection. 5-APDB produced an early depressant phase (ED₅₀ = 3.38 mg/kg) followed by a modest stimulant phase (ED₅₀ = 2.57 mg/kg) 20 to 50 min after injection. In the drug discrimination tests, 5-APDB (ED₅₀ = 1.02 mg/kg), 5-MAPB (ED₅₀ = 1.00 mg/kg) and 6-APB (ED₅₀ = 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.

Keywords: Cocaine; Drug discrimination; MDMA; Methamphetamine; Rats.