Attenuation by dextromethorphan on the higher liability to morphine-induced reward, caused by prenatal exposure of morphine in rat offspring

Ling-Yi Wu,Jain-Fang Chen,Eagle Yi-Kung Huang,Pao-Luh Tao

doi:10.1186/1423-0127-16-106

Ling-Yi Wu, Jain-Fang Chen + Show 2 more

Open Access

https://doi.org/10.1186/1423-0127-16-106

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Abstract

Co-administration of dextromethorphan (DM) with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on morphine-induced reward and behavioral sensitization (possibly related to the potential to induce morphine addiction) in morphine-exposed offspring. Conditioned place preference and locomotor activity tests revealed that the p60 male offspring of chronic morphine-treated female rats were more vulnerable to morphine-induced reward and behavioral sensitization. The administration of a low dose of morphine (1 mg/kg, i.p.) in these male offspring also increased the dopamine and serotonin turnover rates in the nucleus accumbens, which implied that they were more sensitive to morphine. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Thus, DM may possibly have a great potential in the prevention of higher vulnerability to psychological dependence of morphine in the offspring of morphine-addicted mothers.

Highlights

Growth retardation, delayed motor development and behavior abnormalities have been proposed in offspring of heroin-addicted mothers [1]
Chronic morphine administration of the dams caused a more sensitive response to reward of morphine in the offspring rats, which could be prevented by the coadministration of DM in the dams As shown in Fig. 2, the time spent in the drug-associated compartment minus the time spent in the saline-associated compartment was expressed as place preference induced by drugs
Before conditioning, p60 rats of the control group showed no significant place preference (32 ± 47.6 sec) for the drug-associated compartment, which indicated that the conditioned place preference (CPP) apparatus that we used was of a non-biased design [13]

Summary

Introduction

Growth retardation, delayed motor development and behavior abnormalities have been proposed in offspring of heroin-addicted mothers [1]. We observed that many adverse effects caused by prenatal exposure of morphine could be prevented by the coadministration of dextromethorphan (DM) in morphinedependent rat dams [5,6]. The possible impacts of prenatal exposure of morphine on the vulnerability to drug addiction have seldom been examined. The liability to opioid dependence can be affected by acquired physical conditions and social factors in offspring from morphine-addicted mother. We attempted to investigate the possible effects of prenatal exposure to morphine on the vulnerability to morphineinduced reward in an animal model of rats. The possible protective effect of the co-administered DM was tested

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