Quantitative trait loci (QTLs) mapping has been performed during the past decades in an attempt to identify genes, gene products and mechanisms underlying numerous quantitative traits. It's a strategy based on natural variations in genes and gene products, which facilitates translation from animal models to human clinical conditions. Our team has shown that the inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) differ with respect to several emotionalityrelated behaviors, one of which (inner locomotion in the open field) was strongly influenced by a QTL (Anxrr16) on rat chromosome 4. Since then, several other studies not only corroborated the initial description of Anxrr16, but also extrapolated its effects to a broader context (rats from both sexes and regardless of the estrous cycle phase) and suggested that this same region influences other emotionality-related behaviors as well as alcohol intake. Other QTLs affecting neurobiological traits were also found on rat chromosome 4 and several candidate genes have been pointed out as possibly influencing those phenotypes. Altogether, these studies suggest that rat chromosome 4 constitutes an interesting target for the study of the molecular bases of anxiety and other traits related to emotional reactivity.

The Lewis (LEW) and SHR (Spontaneously Hypertensive Rats) inbred rat strains differ in several anxiety/emotionality and learning/memory-related behaviors. We aimed to search quantitative trait locus (QTL) that influence these behaviors and confirm their effects in a congenic rat strain SLA16 (SHR.LEW.Anxrr16). LEW females and SHR males were intercrossed to produce F2 rats (96/sex), which were all tested in the plus-maze discriminative avoidance task (PMDAT), open-field (OF), object recognition (OR), spontaneous alternation (SA) and fear conditioning (FC). All animals were genotyped for microsatellite markers located on chromosome (Chr) 4. Behavioral and genotypic data were used to perform factor and QTL analyses. Also, to confirm the QTL effects, we tested male and female SLA16 rats and their isogenic control SHR in the same behavioral tests. A factor analysis of the F2 population revealed a correlation between anxiety/emotionality related behaviors and learning/memory in both sexes. QTL analysis revealed two significant QTL in males and three in females, on behavioral parameters in the PMDAT, OF and FC. Four QTL found herein were confirmed in SLA16 rats. The SLA16 strain displayed lower levels of anxiety/emotionality, higher locomotor activity and deficits in learning/memory in comparison with SHR strain. The Chr 4 contains genes influencing anxiety/emotionality and learning/memory behaviors and the SLA16 strain represents a valuable tool in the search for them. The use of the SLA16 strain as a genetic model for studying behavioral phenomena and their implications for psychiatric disorders are discussed.