Galnon facilitates extinction of morphine-conditioned place preference but also potentiates the consolidation process.

Xiaojie Zhao,Zhenyuan Wang,Keming Yun,Ronald R Seese

doi:10.1371/journal.pone.0076395

Abstract

Learning and memory systems are intimately involved in drug addiction. Previous studies suggest that galanin, a neuropeptide that binds G-protein coupled receptors, plays essential roles in the encoding of memory. In the present study, we tested the function of galnon, a galanin receptor 1 and 2 agonist, in reward-associated memory, using conditioned place preference (CPP), a widely used paradigm in drug-associated memory. Either before or following CPP-inducing morphine administration, galnon was injected at four different time points to test the effects of galanin activation on different reward-associated memory processes: 15 min before CPP training (acquisition), immediately after CPP training (consolidation), 15 min before the post-conditioning test (retrieval), and multiple injection after post-tests (reconsolidation and extinction). Galnon enhanced consolidation and extinction processes of morphine-induced CPP memory, but the compound had no effect on acquisition, retrieval, or reconsolidation processes. Our findings demonstrate that a galanin receptor 1 and 2 agonist, galnon, may be used as a viable compound to treat drug addiction by facilitating memory extinction process.

Highlights

Drug addiction, characterized by persistent drug-seeking behaviors, is frequently conceptualized as a disorder of maladaptive memory [1,2]
The degree of conditioned place preference (CPP) induced by morphine was significantly different than that in animals injected with either galnon or saline (5 mg-galnon vs 5 mg-morphine (n = 8), p,0.001; saline vs 5 mg-morphine, p = 0.001; Fig. 1B)
The present study examined the effect of galnon, a galanin receptor 1 and 2 agonist, on morphine-induced reward memory using the CPP paradigm

Summary

Introduction

Drug addiction, characterized by persistent drug-seeking behaviors, is frequently conceptualized as a disorder of maladaptive memory [1,2]. Once re-exposed to drug-associated environmental cues, drug-seeking behavior can be reactivated and relapse may occur after years of abstinence. Persistent and unwanted drug-associated memory is believed to be a key contributor to this chronic relapse problem. The neuropeptide galanin was suggested to play an important role in addictive behaviors [5,6]. The neuropeptide has been more directly implicated in drug addiction as galanin knockout (KO) mice (GAL 2/2) show increased sensitivity to morphine and cocaine but decreased sensitivity to nicotine in the conditioned place preference (CPP) paradigm; locomotor activity is robustly hyperactive following morphine administration in GAL

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Conclusion