Cannabinoid-Elicited Conditioned Place Preference in a Modified Behavioral Paradigm

Abstract

Cannabinoids are the active ingredients in marijuana, which is among the most widely used addictive drugs despite the well-documented harmfulness related to its abuse. The mechanism underlying cannabinoid addiction remains unclear, which is attributed partially to the difficulty in behavioral testing of high-dose cannabinoids using the conditioned place preference (CPP) model. Here, we optimized conditions for establishing CPP with the synthetic cannabinoid HU210 intraperitoneally administered at a high dose. We found that the natural place preference of rats could be exploited for establishing a biased CPP model, and that the adverse effect of HU210 could be ameliorated by adding four daily pre-injections before the conditioning program. Thus, 0.1 mg/kg HU210 induced CPP when pre-injections were administered before traditional conditioning with HU210 administration paired with the non-preferred compartment. The present study provides a useful CPP model for behavioral measurement of the rewarding effects of cannabinoids.