A Strategy to Prioritize Emerging Drugs of Abuse for Analysis: Abuse Liability Testing Using Intracranial...

Area of Science:

• Neuroscience
• Pharmacology
• Forensic Science

Background:

• Novel psychoactive substances (NPS) present significant public health and forensic challenges.
• Limited resources necessitate efficient methods for prioritizing NPS abuse liability testing.

Purpose of the Study:

• To introduce and validate a preclinical strategy for prioritizing NPS based on abuse potential.
• To assess the abuse liability of the synthetic cathinone α-PHP using intracranial self-stimulation (ICSS).

Main Methods:

• Male Sprague-Dawley rats underwent surgical implantation of electrodes targeting the medial forebrain bundle for ICSS.
• Rats were trained to lever-press for brain stimulation and tested with varying doses of α-PHP, cocaine (positive control), and saline (negative control).

Main Results:

• Saline and low-dose α-PHP did not alter ICSS responding.
• Higher doses of α-PHP (1.0 and 3.2 mg/kg) and cocaine (10 mg/kg) significantly facilitated ICSS responding.
• The ICSS profile indicated high abuse potential for α-PHP, with rapid onset and long duration.

Conclusions:

• Intracranial self-stimulation (ICSS) effectively distinguishes between compounds with low and high abuse potential.
• The findings support the scheduling of α-PHP and propose ICSS as a valuable tool for screening and prioritizing emerging NPS.
• A four-category priority classification strategy for NPS using ICSS is proposed.