Cannabinoid receptor type 1 agonist disrupts methamphetamine-induced conditioned place preference in adolescent male rats

Abstract

Addiction can be viewed as a state of compulsive engagement in drug use. It is believed that drug-associated memories maintain compulsive drug-seeking behavior. Therefore, disrupting drug-associated memories may reduce drug-seeking behavior. In the present study, a conditioned place preference (CPP) apparatus was conducted to evaluate the effect of cannabinoid receptor type 1 (CB1R) agonist and antagonist on the acquisition of CPP induced by methamphetamine (METH). Anxiety behaviors and memory retrieval were assessed using elevated plus maze (EPM) and step-through passive avoidance tasks. In this study using a 5-day schedule of CPP, exposure to METH increased the time spent in the drug-paired compartment, and CB1Rs agonist (WIN 55,212–2, WIN) disrupted the METH-induced CPP. In the EPM experiment, METH significantly decreased the ratio of times spent in the open arms to total times spent in any arms (OAT) and the ratio of entries into open arms to total entries (OAE), indicating that METH increases anxiety-like behaviors. However, CB1Rs antagonist (SR141716A, SR) reversed METH-induced anxiety behaviors. The results obtained in the passive avoidance experiment showed that blockade of brain CB1Rs by SR improves METH-induced amnesia. In summary, it seems that CB1Rs play a modulatory role in METH-associated memories and CB1Rs antagonist can be a therapeutic target for METH-induced anxiety behaviors.