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A Strategy to Prioritize Emerging Drugs of Abuse for Analysis: Abuse Liability Testing Using Intracranial Self-stimulation (ICSS) in Rats and Validation with α-pyrrolidinohexanophenone (α-PHP)

NCJ Number
Emerging Trends in Drugs, Addictions, and Health Volume: 1 Dated: 2021
Date Published
8 pages

This article proposes a new strategy for identifying and prioritizing novel psychoactive substances (NPS) using intracranial self-stimulation (ICSS) in order to quickly assess the threat to public health and safety and reduce strain on forensic resources.


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, the authors 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. (Published Abstract Provided)

Date Published: January 1, 2021