Effect of chronic intracerebroventricular administration of an aromatase inhibitor on the expression of socio-sexual behaviors in male Japanese quail

Abstract

Aromatase converts androgens into estrogens in the brain of vertebrates including humans. This enzyme is also expressed in other tissues where its action may result in negative effects on human health (e.g., promotion of tumor growth). To prevent these effects, aromatase inhibitors were developed and are currently used to block human estrogen-dependent tumors. In vertebrates including quail, aromatase is expressed in a highly conserved set of interconnected brain nuclei known as the social behavior network. This network is directly implicated in the expression of a large range of social behaviors. The primary goal of this study was to characterize in Japanese quail the potential impact of brain aromatase on sexual behavior, aggressiveness and social motivation (i.e., tendency to approach and stay close to conspecifics). An additional goal was to test the feasibility and effectiveness of long-term delivery of an aromatase inhibitor directly into the third ventricle via Alzet™ osmotic minipumps using male sexual behavior as the aromatase dependent measure. We demonstrate that this mode of administration results in the strongest inhibition of both copulatory behavior and sexual motivation ever observed in this species, while other social behaviors were variably affected. Sexual motivation and the tendency to approach a group of conspecifics including females clearly seem to depend on brain aromatase, but the effects of central estrogen production on aggressive behavior and on the motivation to approach males remain less clear.

Keywords: Aggressive behavior; Aromatase; Bird; Neurosestrogen; Sexual behavior; Social motivation.

Figure 1.

Effect of central inhibition of aromatization on the expression of copulatory behavior in gonadally intact males. Data from each test (T1 to T7) were analyzed by separate Mann-Whitney U test followed by Bonferroni correction: (*)p_cor<0.10, *p_cor<0.05, **p_cor<0.01. MA: mount attempt, CCM: cloacal contact movement.

Figure 2.

Effect of central inhibition of aromatization on the expression of copulatory behavior in castrated males chronically treated with testosterone. Data are presented for the 8 pretests and 6 tests performed after osmotic pump implantation. Data from each test were analyzed by separate Mann-Whitney U test followed by Bonferroni correction: (*) p_cor<0.10, *p_cor<0.05, **p_cor<0.01, ***p_cor<0.001. MA: mount attempt, CCM: cloacal contact movement.

Figure 3.

Effect of central inhibition of aromatization on the rhythmic cloacal sphincter movement (RCSM) frequency in response to the view of a female (A) or a male (B) stimulus and comparison of the RCSM produced by the vehicle males in response to the two stimuli (C). Data in A and B were analyzed by two-way ANOVA with the two phases of the test as a repeated measure and the treatment as an independent factor followed by Sidak’s post-hoc tests when the interaction was significant. Data in C were analyzed by paired t test. (*)p<0.10, **p<0.01,***p<0.001.

Figure 4.

Effect of central inhibition of aromatization on the rhythmic cloacal sphincter movement (RCSM) frequency in response to the view of a female stimulus in castrated testosterone-treated males. Tests were performed before implantation of the osmotic pumps filled with vehicle or vorozole (VOR) (Pre-test, A) and 2 (Test 1 (T1; B) or 18 (T2; C) days post-surgery. Individual variations for the vorozole treated birds were also plotted over time (D). Data from each test (A to C) were analyzed by two-way repeated measures ANOVA. Data from panel D were analyzed by one-way repeated measure ANOVA followed by Sidak’s post-hoc tests. (*)p<0.10, ***p<0.001.

Figure 5.

Effect of central inhibition of aromatization on two markers of aggressiveness: the time spent near a glass partition located in front of a male stimulus (A) and the pecking frequency produced in response to the view of a male (B). Data were analyzed by two-way repeated measure ANOVA that identified no significant effect of the treatments, the test conditions and their interaction.

Figure 6.

Effect of central inhibition of aromatization on the expression of male-male behavioral interactions. Males infused with vorozole (VOR) rarely interacted with the castrated male stimulus, while vehicle infused males (VEH) exhibited neck grabs (NG), mount attempts (MA), mounts (M) and occasionally contact cloacal movements (CCM). Mann-Whitney U-test: (*)p<0.10, **p<0.01,***p<0.001.

Figure 7.

Effect of the inhibition of central aromatization on measures of the sex partner preference of male quail. The preference was quantified during 4 tests (T1 to T4) and preference scores observed during phase 2 of each test (5 min) when the experimental male could approach either the female or the male stimuli were compared by Mann Whitney tests that identified no significant effect of treatment.

Figure 8.

Effect of central aromatase inhibition on social motivation. The experiments assessed the time spent near a group of three gonadally intact females and one gonadally intact male versus an empty compartment (Exp. 1; A) and the time spent near a group of three castrated males and one gonadally intact male versus an empty compartment (Exp. 2; B). In experiment 2 (panel B), birds were tested before and after being implanted with the osmotic pump delivering vorozole (VOR) or its vehicle (VEH). Mann-Whitney U-test: **p<0.01