LONG TERM EFFECTS OF THE INHIBITION OF BRAIN AROMATASE ON THE EXPRESSION OF SOCIO-SEXUAL BEHAVIORS IN MALE JAPANESE QUAIL

Aromatase converts androgens into estrogens in the brain of vertebrates including humans [2]. This enzyme is also expressed in other tissues [8] 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 [3] but their central effects are poorly known in humans. In vertebrates including quail, aromatase is expressed in a highly conserved set of interconnected brain nuclei known as the social behavior network [5,7]. This network is directly implicated in the expression of a large range of social behaviors.
Given the potential implication of brain aromatase in a variety of behavioral processes, the primary goal of this study was to characterize in Japanese quail the potential impact of brain aromatase irrespective of its neuroanatomical location on sexual behavior, aggressiveness and social motivation (i.e., tendency to approach and stay close to conspecifics). The Japanese quail (Coturnix japonica) is an excellent experimental model to analyze the functions of brain aromatase since males of this species exhibit a dense expression of this enzyme in most nuclei of the social behavior network [4] and they display a large range of social behaviors in laboratory settings [1,6]. A secondary goal was to test the feasibility of long-term delivery of an aromatase inhibitor directly into the third ventricle via Alzet™ osmotic minipumps.
Adult male quail were implanted with a 200µl osmotic pump (Alzet®, Model 2004, 0.25µl per hour, 28 day expected duration) connected by a 25cm vinyl cannula tubing (C312VT; 0.69 x 1.14 mm; PlasticsOne®) to a single guide osmotic brain cannula (3220P/SPC, Cut 8 mm below pedestal; PlasticsOne®) implanted in the third ventricle. The osmotic pumps were loaded with either the aromatase inhibitor, vorozole™ (R76713 or VOR, Janssen Pharmaceutica, Beerse, Belgium; 50µg/µl in propylene glycol) or with the vehicle (propylene glycol) under sterile conditions. Birds were either sexually mature gonadally intact birds (Experiment 1) or had been castrated and treated with exogenous testosterone via a subcutaneous Silastic implant (Experiment 2). They were then tested over a period of about 3 weeks for a variety of social behavior including consummatory sexual behavior, appetitive sexual behavior assessed by the frequency of rhythmic cloacal sphincter movements (RCSM), aggressive behavior, sex partner preference, and social reinstatement motivation. These last two behaviors were measured in a 5-compartment corridor by quantifying the time spend near stimuli (male, female or groups of conspecifics) placed at the two ends.