Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants.
Abstract
<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>In the locomotor activity test, MDMA (ED<sub>50</sub> = 8.34 mg/kg) produced peak stimulant effects 60 to 80 min following injection. 5-MAPB (ED<sub>50</sub> = 0.92 mg/kg) produced modest stimulant effects 50 to 80 min after injection, whereas 6-APB (ED<sub>50</sub> = 1.96 mg/kg) produced a robust stimulant effect 20 to 50 min after injection. 5-APDB produced an early depressant phase (ED<sub>50</sub> = 3.38 mg/kg) followed by a modest stimulant phase (ED<sub>50</sub> = 2.57 mg/kg) 20 to 50 min after injection. In the drug discrimination tests, 5-APDB (ED<sub>50</sub> = 1.02 mg/kg), 5-MAPB (ED<sub>50</sub> = 1.00 mg/kg) and 6-APB (ED<sub>50</sub> = 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.<h4>Conclusions</h4>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.
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