The serotonin transporter (SERT) has been associated with mood and anxiety-related disorders both because it is a primary molecular target of many widely prescribed antidepressants (SRIs, tricyclics) and because human SERT gene variants associated with lower SERT expression have been correlated with vulnerability to stress-associated depression.
We have recently shown that aging female (but not male) mice with intermediate reductions in SERT expression (SERT+/-) exhibit increased anxiety-like behavior in the elevated plus maze. In this study, aging SERT deficient mice were exposed to the marble burying task to assess further whether modest changes in SERT expression influence anxietyrelated
behaviors. SERT+/- and wildtype (SERT+/+) mice of both sexes (24 months of age) were placed individually in plastic cages containing 5 cm of sawdust bedding with marbles placed on top of the bedding and evenly spaced. After 30 minutes, mice were removed and the number of unburied, partly buried and fully buried marbles was counted. A marble was considered buried if it was two-thirds underneath the sawdust. Mice were maintained on a 12 h day/night cycle (lights on at 0600) with behavioral testing beginning at 1900 h. Three trials were conducted with 3 days between trials to determine the number of marbles buried when animals were exposed to 15, 20, and 25 total marbles. SERT+/+ mice buried on average 6, 8, and 10 marbles, respectively, while SERT+/- mice buried 8, 12, and 17 marbles, respectively.
These results suggest that overall, mice bury increasing numbers of marbles as a function of marbles available and that this behavior is amenable to repeated measures design. Furthermore, SERT+/- mice buried more marbles in all three trials possibly reflecting increased anxiety-like behavior. On the last trial, mice were injected with 10 mg/kg fluoxetine, and then underwent the marble burying task (15 total marbles) one hour later. Although previous studies have reported an inhibition of marble burying after SRI administration, we observed an increase in marble burying in SERT+/+ mice of both sexes and male SERT+/- mice. By contrast, female SERT+/- mice exhibited a decrease in the number of marbles buried. This preliminary study suggests that the marble burying task may be a useful measure of anxiety-related behavior in aging mice and that female SERT+/- mice exhibit antidepressant-sensitive decreases in anxiety-like behavior. Further studies will be conducted to examine the role of SERT in this task at younger ages, as well as the influence of antidepressants during marble burying behavior.