Delta-opioid receptor antagonism leads to excessive ethanol consumption in mice with enhanced activity of the endogenous opioid system

Review of research on alcohol dependence in a model of mice selected for high and low stress-induced analgesia

“…Ethanol ingestion had an anti-depressive and anxiolytic effect making individuals feel better and leading to uncontrolled ethanol consumption. This result is very interesting, as it points to a danger of using other non-selective antagonist of the opioid system -naltrexone, which is FDA approved drug in the therapy of alcohol-dependent patients [11]. However, stimulation of this receptor system by morphine caused slight attenuation of ethanol self-administration in both lines, but in the HA mice, the effect was more pronounced [Unpublished data].…”

“…Moreover, the administration of NTI to CT heterozygotes of both lines caused no effect, despite their higher basal ethanol preference. It has been proven that C320T transition causes dysfunction of the DOR, resulting in the absence of NTI effect on ethanol consumption [10,11]. While comparing the studies by Sacharczuk et al and Poznanski et al, different degree in response to congenital dysfunction and pharmacological blockage between HA and LA mice is explained by the possibility of compensation of delta opioid receptors dysfunction by mu opioid receptors in HA individuals with C320T transition, hence the genetic effect is more significant in LA mice.…”

“…The latest study performed on these divergently selected mouse lines focused on determining the role of endogenous opioid system activity and the subtypes of opioid receptors in the development of alcohol dependence [11]. Non-selective pharmacological antagonism of the opioid system by intraperitoneal administration of naloxone (NLX) resulted in a drastic increase of ethanol intake and preference in mice with a hyperactive opioid system.…”

“…While comparing the studies by Sacharczuk et al and Poznanski et al, different degree in response to congenital dysfunction and pharmacological blockage between HA and LA mice is explained by the possibility of compensation of delta opioid receptors dysfunction by mu opioid receptors in HA individuals with C320T transition, hence the genetic effect is more significant in LA mice. Additionally, pharmacological antagonism is 'artificial' at a specific point in time, thus there is no compensation mechanism established, and effect of the pharmacological blockade is more significant in HA mice [10,11].…”

“…The impact of the opioid system neurotransmission on the development and course of alcohol dependence is well-documented, hence experiments in which mouse characterised by high and low endogenous opioid system activity are used may help in better understanding of its role in the addiction process or trying to develop some new pharmacotherapies [3,8]. This model is well documented in the subjects with alcohol dependence [9,10,11], effects of chronic mild stress (CMS) [12], melanoma growth [13,14], and morphine efficacy [15]. It was developed on the basis of differences in the level of stress-induced analgesia (SSIA) resulting from the opioid system activity [16].…”