The Involvement of GLT‐1 in The Drug Seeking Like Effects of Pregabalin

Abstract

Pregabalin is a GABA analogue that can bind with high affinity to voltage‐gated calcium channel to minimize excitatory neurotransmitters release. However, several case reports in Middle East and other parts of the world raised the concern of its abuse potential. We have shown in our previous studies that higher doses of pregabalin can cause drug seeking like effect in conditioned place preference (CPP) mouse model. In this study, we tested the involvement of glutamate transporter 1 (GLT‐1), which has a significant role in glutamate homeostasis and in mediating the rewarding and drug seeking effects of several drugs of abuse. Male BALB/c mice were randomly separated into four groups; the control group (C‐C) received saline in home cages and during the conditioning training. The second group (CEF‐C) received ceftriaxone (CEF) in a dose that was consistently shown to upregulate GLT‐1, (200 mg/kg, i.p.), in home cages and received saline during conditioning training. The third group (C‐Preg) received saline in home cages and were administered pregabalin in a dose that previously shown to induce CPP (60 mg/kg) during conditioning training. The last group (CEF‐Preg) received CEF in home cages and injections of pregabalin during the conditioning training. Consistent with our previous studies, the time spent in drug‐paired chamber as compared to the vehicle‐paired chamber was significantly increased in C‐Preg group. Importantly, CEF treatment for eight days blocked pregabalin induced CPP. These results showed for the first time the possible involvement of GLT‐1 in mediating the rewarding effects of pregablin in animal model of drug addiction.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.