Further studies on the effects of acamprosate on tolerance to the analgesic effects of morphine and NO synthesis in the brain

Jacqueline Sepúlveda,Enrique Contreras,Jorge Roa,Andrea Ortega

doi:10.4236/health.2013.511a1001

Abstract

The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme responsible for neuronal NO synthesis (nNOS) in the nucleus accumbens (NAc) of mice chronically treated with morphine and during the abstinence syndrome induced by naloxone. The enzyme was monitored by the NADPH diaphorase method. The number of cells stained for NADPH diaphorase in the NAc of mice was counted in 40 μm thick coronal brain slices at 40X. The intensity of the histochemical reaction of stained cells from naive morphine plus saline and morphine plus acamprosate treated mice was analyzed by Image Pro Plus 4.5.1. Morphine administered in a slow release preparation increased the stain intensity of the positive neurons. The increase in the NADPH staining persisted after naloxone was given to mice chronically treated with morphine. Acamprosate antagonized the effects induced by chronic morphine treatment in the NAc of mice. These results indicate that up-regulation of nNOS in the NAc is a consequence of the sustained effects of morphine stimulation, which, in turn, may result from an increased in glutamate release during the abstinence syndrome.

Highlights

Acamprosate is a taurine analog that has received considerable attention for its ability to prevent relapse in abstinent alcoholics [1,2,3,4,5]
No significantly changes were found in the number of NADPH positive neurons in the nucleus accumbens (NAc) of mice treated with morphine, acamprosate, either alone or in combination with the opiate, when compared to the results observed in naive mice or in control animals injected with saline or vehicle
No differences in the number of NADPH positive neurons were observed in morphine dependent mice at the end of the chronic morphine treatment or after naloxone administration (Figure 1)

Summary

Introduction

Acamprosate is a taurine analog (calcium acetylhomotaurinate) that has received considerable attention for its ability to prevent relapse in abstinent alcoholics [1,2,3,4,5]. It has been demonstrated that the drug reduces Ca2+ fluxes through voltage-operated channels and that it interacts with NMDA receptor-mediated glutamatergic neurontransmission in various brain regions with functional antagonistic properties [6,7,8]. The NAc is thought to be a determinant structure of the brain for the expression of rewarding effects of opiates [11,12]; neurochemical studies have demonstrated that the acute administration of morphine affects the concentrations of dopamine [13] acetylcholine [14], and that chronic morphine administration in rats augments glutamate release in the NAc, and in morphine-tolerant rats following naloxone administration [15]

Objectives

Methods

Results

Conclusion