Invited reviewRat animal models for screening medications to treat alcohol use disorders
Section snippets
Societal burden of alcohol abuse and dependence
Approximately half of all Americans have at least one relative with an alcohol use disorders (AUD), with some of these individuals having this trait across multiple generations (Research Society on Alcoholism, 2011, Research Society on Alcoholism, 2015). Half of individuals meeting a life-time diagnosis for an AUD do so by age 21 with two-thirds doing so by age 25 (Hingson et al., 2006). This is especially troubling given between 15% and 25% of individuals in the military have AUDs (Bray and
Pros and cons of animal model research
While drug development relies heavily on in vitro assays early in the process, subsequent studies in vivo are required in the pathway to FDA regulation and clinical use (Blass, 2015). In vivo assays are required to evaluate a compound in a highly complex biological system as opposed to in vitro assays, which are constrained by their limited macromolecular environment (Blass, 2015). Essentially, the outcome measures of an in vivo assay are greater than the sum of its multiple constituent
Selective breeding
Bi-directional selective breeding is a powerful genetic tool that has been employed to study the genetics of many ethanol-associated phenotypes (Crabbe, 2010, Crabbe et al., 2010). Compared to pure association studies such as genome-wide association studies (GWAS) and studies using recombinant inbred lines (RILs) panels, selective breeding from a heterogeneous outbred stock can make low frequency/rare alleles more common. Selective breeding involves establishing a distribution of scores for the
The home-cage and operant environments
Home-cage drinking is relatively self-explanatory, such that the rat has access to ethanol in its home-cage environment. There are pros and cons to this test environment and there continues to be a debate as to its face validity with the clinical condition. However, home-cage drinking is positively associated with both the reinforcing and rewarding aspects of ethanol (e.g., Green and Grahame, 2008). On the other hand, operant self-administration requires removing the rat from its home-cage and
Caveats, challenges, and conclusions
A few caveats need to be mentioned before summarizing this review. First, the mouse ethanol research literature was not discussed. This was done due to space limitations and in no way minimizes the substantial literature that is associated with it. Second, transgenic ethanol research was not discussed. Similar to the first caveat, especially since most of the transgenic work has involved mice, this was done due to space limitations. For excellent discussions on both of these subjects see
Statement of conflict
All authors declare they have no perceived or real conflicts of interest associated with any part of this work.
Acknowledgements
The present work was supported in part by NIAAA grants AA07611, AA013522 and AA015512.
References (685)
Circadian drinking rhythms and blood alcohol levels in two rat lines developed for their alcohol consumption
Alcohol
(1986)- et al.
Cocaine self-administration in Warsaw alcohol high preferring (WHP) and Warsaw alcohol low preferring (WLP) rats
Eur. J. Pharmacol.
(2012) - et al.
Development of short-lasting alcohol deprivation effect (ADE) in Sardinian alcohol-preferring rats
Alcohol
(2000) - et al.
Alcohol stimulates motor activity in selectively bred Sardinian alcohol-preferring (sP), but not in Sardinian alcohol-nonpreferring (sNP), rats
Alcohol
(2001) - et al.
Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample
Drug Alcohol Depend.
(2008) - et al.
Effects of ampicillin on cystine/glutamate antiporter and glutamate transporter 1 isoforms as well as ethanol drinking in male P rats
Neurosci. Lett.
(2015) Trajectories of brain development: points of vulnerability or windows of opportunity
Neurosci. Biobehav Rev.
(2003)- et al.
Early-onset drug use and risk of later drug problems
Drug Alcohol Depend.
(1995) - et al.
Suppression of alcohol self-administration and cue-induced reinstatement of alcohol seeking by the mGlu2/3 receptor agonist LY379268 and the mGlu8 receptor agonist (S)-3,4-DCPG
Eur. J. Pharmacol.
(2005) - et al.
Habitual alcohol seeking: modeling the transition from casual drinking to addiction
Neurosci. Biobehav Rev.
(2014)