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Sub-dimensions of Alcohol Use Disorder in Alcohol Preferring and Non-preferring Rats, a Comparative Study

Authors: Domi A.; Stopponi S.; Domi E.; Ciccocioppo R.; Cannella N.;

Sub-dimensions of Alcohol Use Disorder in Alcohol Preferring and Non-preferring Rats, a Comparative Study

Abstract

Recent animal models of alcohol use disorder (AUD) are centered in capturing individual vulnerability differences in disease progression. Here, we used genetically selected Marchigian Sardinian alcohol-preferring (msP) and Wistars rats to apply a multidimensional model of AUD adapted from a previously described DSM-IV/DSM-5 multisymptomatic cocaine addiction model. As proof of concept, we hypothesized that msP rats, genetically selected for excessive drinking, would be more prone to develop dependence-like behavior compared to Wistars. Before exposure of animals to alcohol, we monitored basal anxiety in the elevated plus maze (EPM). Animals were then trained in prolonged operant alcohol self-administration, consisting of 30-min daily sessions for 60 days in total. Each session consisted of two 10-min periods of alcohol reinforcement separated by 10-min interval of non-reinforcement. Following training, we applied three criteria of individual vulnerability for AUD: (1) persistence of lever pressing for alcohol when it was not available; (2) motivation for alcohol in a progressive ratio (PR) schedule of reinforcement; and (3) resistance to punishment when alcohol delivery was anticipated by a foot-shock (0.3 mA). We obtained four groups corresponding to the number of criteria met (0-3 crit). Rats in the 0crit and 1crit groups were characterized as resilient, whereas rats in the 2crit and 3crit groups were characterized as prone to develop a dependent-like phenotype. As predicted, the 2-3crit groups were enriched with msP rats while the 0-1crit groups were enriched in Wistar rats. In further analysis, we calculated the global addiction score (GAS) per subject by the sum of the normalized score (z-score) of each criterion. Results showed GAS was highly correlated with animal distribution within the 3 criteria. Specifically, GAS was negative in the 0-1crit groups, and positive in the 2-3crit groups. A positive correlation between basal anxiety and quantity of alcohol intake was detected in msP rats but not Wistars. In conclusion, we demonstrated that the 0/3criteria model is a suitable approach to study individual differences in AUD and that msP rats, selected for excessive-alcohol drinking, show a higher propensity to develop AUD compared to non-preferring Wistars.

Country
Italy
Keywords

alcoholism, Cognitive Neuroscience, Neurosciences. Biological psychiatry. Neuropsychiatry, punished responding, DSM-5, alcohol-seeking, Behavioral Neuroscience, Neuropsychology and Physiological Psychology, ethanol, self-administration, RC321-571, Neuroscience

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    21
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
21
Top 10%
Average
Top 10%
Green
gold