Oxytocin receptor signaling contributes to olfactory avoidance behavior induced by an unpleasant odorant

Abstract

Oxytocin (OXT) and its receptor (OXTR) regulate reproductive physiology (i.e. parturition and lactation), sociosexual behavior, learned patterns of behavior and olfactory behavior in social contexts. To characterize the function of OXTR in basic olfactory behavior, the present study compared the behavioral responses of homozygous, heterozygous and wild-type mice when these mice were confronted with an unpleasant odorant (butyric acid) in a custom-made Y-maze in the absence of a social context. Wild-type mice avoided the first encounter with the butyric acid odorant, whereas homozygous and heterozygous mice did not. However, both heterozygous and wild-type mice habituated when confronted with the butyric odorant again on the following 2 days. By contrast, homozygous mice failed to habituate and instead avoided the location of the odorant for at least 3 days. These data suggest that homozygous and heterozygous mice display abnormal olfactory responses to the presentation of an unpleasant odorant. Our studies demonstrate that OXTR plays a critical role in regulating olfactory behavior in the absence of a social context.

Keywords: Avoidance; Butyric acid; Olfactory behavior; Oxytocin receptor; Y-maze.

Fig. 1.

Homozygous (OXTR-deficient) and heterozygous mice show normal anxiety-like behavior and locomotion. Anxiety (A) was measured by determining the amount of time spent in the central area of an open-field apparatus for up to 5 min. (B) Locomotor activity was measured as a signal produced by the movement of mice on an Animex activity meter within 5 min.

Fig. 2.

Changes in the results of the avoidance test over time. Data from homozygous (closed circle), heterozygous (gray triangle), and wild-type (open square) mice. To show the avoidance rate correctly, the Y-axis shows values between 40–70%. The statistical significance of the differences in the avoidance rates of the three groups was assessed using two factors repeated-measure ANOVA followed by Bonferroni post-hoc test (*P<0.05, **P<0.01), different letters between the groups indicate a significant difference (P<0.05).

Fig. 3.

Comparison of time changes in avoidance rates between males and females. Data for (A) wild-type, (B) heterozygous and (C) homozygous mice are presented. The Y-axis shows values between 40–70%. The statistical significances of the differences between the avoidance rates of males (gray column) and females (open column) were assessed using repeated-measure ANOVA followed by Bonferroni post-hoc test.

Fig. 4.

Comparison between the control trial and trial 1. Data for (A) wild-type, (B) heterozygous and (C) homozygous mice are presented. The rate at which mice avoided the unpleasant butyric acid odorant in the Y-maze, that is, the avoidance rate, of trial 1 was taken to be the amount of time spent in the short arm containing the control odorant divided by the total amount of time spent in both short arms (control versus butyric acid), multiplied by 100. Water was substituted for butyric acid in control experiments (control versus control). Values are the mean±s.e.m. of at least eight animals in each group. The statistical significance of the differences between the avoidance rates was assessed using the paired t-test. Wild type, P=0.001; heterozygous, not significant (NS); homozygous, NS.