REVIEW: The alcohol‐preferring AA and alcohol‐avoiding ANA rats: neurobiology of the regulation of alcohol drinking

Laboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, USA.
Addiction Biology (Impact Factor: 5.36). 10/2006; 11(3-4):289-309. DOI: 10.1111/j.1369-1600.2006.00037.x
Source: PubMed


The AA (alko, alcohol) and ANA (alko, non-alcohol) rat lines were among the earliest rodent lines produced by bidirectional selection for ethanol preference. The purpose of this review is to highlight the strategies for understanding the neurobiological factors underlying differential alcohol-drinking behavior in these lines. Most early work evaluated functioning of the major neurotransmitter systems implicated in drug reward in the lines. No consistent line differences were found in the dopaminergic system either under baseline conditions or after ethanol challenges. However, increased opioidergic tone in the ventral striatum and a deficiency in endocannabinoid signaling in the prefrontal cortex of AA rats may comprise mechanisms leading to increased ethanol consumption. Because complex behaviors, such as ethanol drinking, are not likely to be controlled by single factors, system-oriented molecular-profiling strategies have been used recently. Microarray based expression analysis of AA and ANA brains and novel data-mining strategies provide a system biological view that allows us to formulate a hypothesis on the mechanism underlying selection for ethanol preference. Two main factors appear active in the selection: a recruitment of signal transduction networks, including mitogen-activated protein kinases and calcium pathways and involving transcription factors such as Creb, Myc and Max, to mediate ethanol reinforcement and plasticity. The second factor acts on the mitochondrion and most likely provides metabolic flexibility for alternative substrate utilization in the presence of low amounts of ethanol.

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Available from: Wolfgang H Sommer, Jun 30, 2015
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    • "However, as opposed to the human condition, these animals tolerate high amounts of alcohol well. In fact, it seems as if their physical wellbeing and life span is not influenced by chronic alcohol consumption, which is likely due to high metabolic flexibility in the use of alcohol (Sarviharju et al. 2004; Björk et al. 2006; Sommer, Hyytiä & Kiianmaa 2006). The second category is based on alcohol-induced neuroadaptations acknowledging the fact that drug addiction inevitably requires drug exposure. "
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    ABSTRACT: Rational development of novel therapeutic strategies for alcoholism requires understanding of its underlying neurobiology and pathophysiology. Obtaining this knowledge largely relies on animal studies. Thus, choosing the appropriate animal model is one of the most critical steps in pre-clinical medication development. Among the range of animal models that have been used to investigate excessive alcohol consumption in rodents, the postdependent model stands out. It was specifically developed to test the role of negative affect as a key driving force in a perpetuating addiction cycle for alcoholism. Here, we will describe our approach to make rats dependent via chronic intermittent exposure to alcohol, discuss the validity of this model, and compare it with other commonly used animal models of alcoholism. We will summarize evidence that postdependent rats fulfill several criteria of a ‘Diagnostic and Statistical Manual of Mental Disorders IV/V-like’ diagnostic system. Importantly, these animals show long-lasting excessive consumption of and increased motivation for alcohol, and evidence for loss of control over alcohol intake. Our conclusion that postdependent rats are an excellent model for medication development for alcoholism is underscored by a summary of more than two dozen pharmacological tests aimed at reversing these abnormal alcohol responses. We will end with open questions on the use of this model. In the tradition of the Sanchis-Segura and Spanagel review, we provide comic strips that illustrate the postdependent procedure and relevant phenotypes in this review.
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    • "The distinct separation between the escalation curves of the high and low consuming animals is of particular interest as it has not been observed in other rat strains exposed to the IAE procedure, where a majority of the animals exhibit high ethanol consumption [1], [2]. There are many ethanol self-administration studies have relied upon comparisons between genetically selected high-preferring and non-preferring lines (P vs. NP, sP vs. sNP, AA vs. ANA, or HAD vs. LAD rats) in order to examine phenotypic differences between high and low ethanol-preferring animals [12]–[15]. We have previously shown that intermittent access to ethanol induces an increase in ethanol consumption in Wistar, Long-Evans and P-rats [1], [2]. "
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    • "It has also been shown that early-life environment interact with genetic propensity for high ethanol intake. In the selectively bred alcohol-preferring Alko Alcohol (AA) rats (Bell et al. 2012; Sommer et al. 2006), exposure to MS360 adds to genetic risk and results in increased ethanol intake (Roman et al. 2003, 2005; Fig. 2). AA rats that were subjected to repeated MS15 instead had lower ethanol consumption than AFR AA rats, further pointing to the fact that short periods of maternal absence is beneficial for the offspring and can counteract genetic predisposition for high ethanol consumption (Roman et al. 2003, 2005). "
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