Dose-effect analysis of 6-APB ("Benzofury") on fear memory, motor behavior, and reward.

Abstract

6-(2-aminopropyl)benzofuran (6-APB) is a recreational drug that is structurally similar to MDMA. Very little is known about the behavioral effects of 6-APB or its dose-effect relationship in vivo. As the popularity of new psychoactive substances (NPS), such as 6-APB, increases due to their unscheduled status and easy availability, it is important to understand the potential benefits and/or harms of such substances. The current study aims to establish a dose-effect curve of 6-APB on fear memory, pain sensitivity, motor coordination, and addiction-related behavior in mice. Male and female hybrid C57BL/6Jx129S1/SvImJ mice were used to examine the effects of 0.01 to 5 mg/kg of 6-APB on Pavlovian fear conditioning; flinch, jump, vocalize; Accelerating Rotarod; behavioral sensitization, conditioned place preference, and conditioned responding. We found that 6-APB elicits effects at very low doses (0.01 and 0.1 mg/kg), while impairing short-term fear memory and long-term context memory at a dose of 5 mg/kg. We also observed that 6-APB produces modest locomotor sensitization and may produce addiction. Finally, there is evidence of reduced shock reactivity; this was not likely due to analgesia and more likely due to ataxia produced by the drug. 6-APB produces a behavioral profile broadly similar to MDMA, with amnesic effects emerging at higher doses than MDMA and a larger gap between potential therapeutic doses and doses that produce cognitive deficits. These findings suggest 6-APB may not be the low-risk therapeutic alternative to MDMA currently sought in clinical contexts, though further research is warranted.