Identification of female-specific QTLs affecting an emotionality-related behavior in rats

The influence of genetic factors on psychological traits and disorders has been repeatedly demonstrated; however, the molecular mechanisms underlying such an influence remain largely unknown. Anxiety-related disorders constit ute the most common class of mental disorder in humans, with women being di agnosed far more frequently than men. A better understanding of the genetic and gender-related mechanisms mediating anxiety traits should enable the d evelopment of more rational methods for preventing and treating anxiety dis orders. In this study we have aimed to identify, for the first time, quanti tative trait loci (QTL) influencing anxiety/emotionality-related traits in rats. TO this end, two strains-Lewis (LEW) and Spontaneously Hypertensive R ats (SHR)-that differ for several behavioral measures of anxiety/emotionali ty were intercrossed. A QTL analysis of the F2 population revealed suggesti ve loci for various traits, including behaviors in the elevated plus-maze a nd blood pressure. In addition, one major QTL explaining 50.4% of the total variance (LOD = 7.22) was identified on chromosome 4 for the locomotion in the central and aversive area of the open field. Two other relevant QTLs h ave been recently mapped near this chromosomic region in the rat, which als o harbors Tac1r, the gene encoding for the substance P receptor. Our major QTL affected females but not males and its effect depended on the type of c ross (LEW or SHR grandmothers). The present results reveal a complex geneti c basis underlying emotional behaviors and they confirm the existence of in teractions between genetic factors and sex for this kind of trait. Further investigation of the loci identified herein may give clues to the pathophys iology of psychiatric disorders such as anxiety-related ones.