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Pharmacogenetics. 2003 Sep;13(9):543-54.

Genetics of behaviour: phenotypic and molecular study of rats derived from high- and low-alcohol consuming lines.

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Laboratoire de Neurogénétique et Stress, UMR 1243 INRA--Université Victor Segalen, Inserm U471, Institut François Magendie, Bordeaux, France.


The aim of this study was to analyse the genetic basis of excessive ethanol consumption and its relationship with emotional reactivity. The high-ethanol preferring line of rats used is characterized by a: (i) high voluntary consumption of alcohol; (ii) high sensitivity to taste reinforcement (saccharine, quinine); (iii) high locomotor activity in a novel environment; and (iv) low emotional reactivity, these features being opposite in the Wistar-Kyoto (WKY) rat strain. The F2 population demonstrated a very large variability in these behavioural traits, and factor analysis revealed that these characteristics appear to be largely unrelated to each other. The molecular bases for these differences were investigated by quantitative trait loci (QTL) analysis. For this purpose, the 196 F2 rats were genotyped with regularly distributed markers on the whole genome, and genetic linkage maps were generated for all subsequent QTL analyses. A locus with a maximum LOD score of 7.6 and accounting for approximately 61% of the genetic variance of the trait in the F2 population was detected on chromosome 4 for alcohol drinking. In the same region, we found a QTL related to the reinforcement properties of saccharin, with a significant LOD score of 4.9 and explaining 46% of the variance of the trait. Other significant QTL were found for plus maze behaviour and open field activity on chromosome 1. Current research aims to identify the gene(s) involved.

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