Warsaw Low Preferring Rats Research Articles

Novel candidate genes for alcoholism — transcriptomic analysis of prefrontal medial cortex, hippocampus and nucleus accumbens of Warsaw alcohol-preferring and non-preferring rats

ObjectiveAnimal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain functions, including reward system and addiction. The current study aimed to identify genes that may underlie differential ethanol preference in Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) rats. MethodsMicroarray analysis comparing gene expression in nucleus accumbens (NAc), hippocampus (HP) and medial prefrontal cortex (mPFC) was performed in male WHP and WLP rats bred for differences in ethanol preference. ResultsDifferential and stable between biological repeats expression of 345, 254 and 129 transcripts in NAc, HP and mPFC was detected. Identified genes and processes included known mediators of ethanol response (Mx2, Fam111a, Itpr1, Gabra4, Agtr1a, LTP/LTD, renin-angiotensin signaling pathway), toxicity (Sult1c2a, Ces1, inflammatory response), as well as genes involved in regulation of important addiction-related brain systems such as dopamine, tachykinin or acetylcholine (Gng7, Tac4, Slc5a7). ConclusionsThe identified candidate genes may underlie differential ethanol preference in an animal model of alcoholism. CommentNames of genes are written in italics, while names of proteins are written in standard font. Names of human genes/proteins are written in all capital letters. Names of rodent genes/proteins are written in capital letter followed by small letters.

Effect of repeated treatment with topiramate on the beta-endorphin plasma level in rats selectively bred for high and low alcohol preference

Recent research indicates that topiramate has a role in the treatment of alcohol dependence. Topiramate has multiple mechanisms of action including enhancement of GABA-ergic inhibitory transmission and blocking excitatory glutamate neurotransmission, and modulating voltage-gated sodium and calcium ion channels and inhibiting carbonic anhydrase. In this study, we examined the effect of topiramate on endogenous opioid systems, which have an important role in the development of alcohol dependence. We investigated the beta-endorphin plasma level of animals with high- and low-risks of alcohol dependency after repeated treatment with topiramate. We used the Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) rats, and treated them with topiramate at a dose of 80 mg/kg p.o. for 14 days. In WHP rats treatment with topiramate led to an increase in beta-endorphin plasma levels, which persisted at the same level even after a single injection of alcohol. The level of this peptide with topiramate was lower than in alcohol-injected WHP rats who did not receive topiramate. Beta-endorphin levels in WHP rats after topiramate or topiramate and ethanol treatment were similar to the basal level of this peptide in WLP rats. In WLP rats, topiramate did not prevent the ethanol-induced increase in beta-endorphin plasma level. We propose that administration of topiramate may have different effects on the opioid system involved in dependence according to genetic susceptibilities to alcoholism.

Effect of acute administration of ethanol on beta-endorphin plasma level in ethanol preferring and non-preferring rats chronically treated with naltrexone

An ample support can be found in professional literature for the hypothesis that the endogenous opioid system plays an important role in developing a craving for alcohol. It is well established that people with a genetic deficit of beta-endorphin are particularly susceptible to alcoholism. In our study, we looked into the beta-endorphin plasma level of animals with high- and low-risk of alcohol dependency after repeated treatment with naltrexone, the opioid antagonist known to be effective in the treatment of alcoholism. We used the Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) rats and treated them for 10 days with naltrexone in a dose of 2 mg/kg i.p. One hour before blood collection the rats were injected with a single dose of ethanol. A prolonged naltrexone treatment or a single application of ethanol resulted in the increase of the beta-endorphin plasma level. In the WLP rats repeated naltrexone treatment prevents the ethanol-induced increase in beta-endorphin plasma level. In the WHP rats the level of this peptide was similar to it while they were undergoing the naltrexone treatment or had received a single alcohol injection. This finding supports the proposition that the endogenous opioid system plays an important role in developing a craving for alcohol. It is likely that effectiveness of naltrexone in reducing craving for alcohol results from the attenuation of the rewarding properties of ethanol and restoring the beta-endorphin deficit in reward system.

Changes in the beta-endorphin plasma level after repeated treatment with acamprosate in rats selectively bred for high and low alcohol preference

The aim of this study was to evaluate the beta-endorphin (β-endorphin) plasma level in Warsaw Low Preferring (WLP) and Warsaw high-preferring (WHP) rats after repeated administration of acamprosate, one of most effective drug in the treatment of alcoholism. Treatment with acamprosate in dose 200 mg/kg, p.o. for 10 days induced an increase in plasma β-endorphin levels. A single injection of ethanol also results in the increase of β-endorphin level. Moreover, it was found that single injection of ethanol to WHP rats resulted in lower increase of plasma β-endorphin content in rats earlier treated with acamprosate. In WLP rats, repeated acamprosate treatment prevents the ethanol-induced increase in plasma β-endorphin level. It may be concluded that acamprosate modulates the endogenous opioid system.