The influence of sex and estrous cycle on QTL for emotionality and ethanol consumption

The inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) differ with respect to several emotionality- and ethanol intake-related behaviors, one of which (inner locomotion in the open field; OF) is strongly influenced by a locus (Anxrr16) on chromosome (Chr) 4. We aimed to further investigate the influence of Chr 4 on these behaviors and to evaluate the role of the estrous cycle in QTL expression. LEW females and SHR males were intercrossed to produce F1 and F2 rats (96-97/sex), which were then tested in the OF, light-dark box (LDB), forced swimming test (FST), and an ethanol consumption procedure (ECP). In addition, another group of 96 F2 females were tested in the OF and LDB according to their estrous cycle phase. All animals were genotyped for microsatellite markers located on Chr 4 and two QTL analyses were performed. A factor analysis of the F2 population produced five factors reflecting different behavioral dimensions. QTL analysis revealed five significant loci in males, some of which with pleiotropic effects on behaviors measured in the OF, LDB, and ECP. The second QTL analysis revealed two significant loci in females in diestrous-proestrous and one in females in estrous-metestrous that influence behaviors in the OF and LDB. Results revealed that Anxrr16 and four other new QTL influence emotionality- and ethanol-related behaviors in male rats, whereas Anxrr16 attained suggestive levels only in females in diestrous-proestrous, which raises the need for taking into account factors related to the sex and estrous cycle in behavioral QTL analysis.