Citation

Baird TR, Davies RA, Glennon RA, Peace MR, Negus SS. Emerg. Trends Drugs Addict. Health 2021; 1: e100004.

Copyright

(Copyright © 2021, International Society for the Study of Emerging Drugs, Publisher Elsevier Publishing)

DOI

10.1016/j.etdah.2021.100004

PMID

unavailable

Abstract

Novel psychoactive substances (NPS) threaten public health and safety while also straining the limited resources of forensic laboratories. To efficiently allocate the finite resources available, we propose a new strategy for prioritizing NPS with abuse liability testing using a preclinical behavioral procedure in rats known as intracranial self-stimulation (ICSS). To validate this assay, the recently-scheduled synthetic cathinone α-PHP was compared to cocaine, a mechanistically similar drug of abuse, as a positive control and saline as a negative control. Male Sprague-Dawley rats (n=6) were implanted with electrodes targeting the medial forebrain bundle and trained to respond by lever-press for electrical brain stimulation. The rats were tested with doses of 0.32, 1.0, and 3.2 mg/kg α-PHP as well as 10 mg/kg of cocaine and saline administered by intraperitoneal injection. Neither saline nor 0.32 mg/kg α-PHP altered ICSS response rates compared to baseline levels of responding; however, doses of 1.0 and 3.2 mg/kg α-PHP and 10 mg/kg cocaine facilitated ICSS responding. This ICSS profile suggests that α-PHP has high abuse potential, with a rapid onset of effects and a long duration of action, and supports the decision to schedule this compound. This study demonstrates the ability of ICSS to distinguish between compounds of low and high potential for abuse. A strategy is proposed here to screen NPS using ICSS and classify emerging drugs into four priority categories for further analysis.

Language: en

Keywords

Abuse liability testing; Intracranial self-stimulation; Novel psychoactive substances; Synthetic cathinones; α-pyrrolidinohexanophenone