Androgen insensitive male rats display increased anxiety-like behavior on the elevated plus maze.

Male rats carrying the testicular feminization mutation (Tfm-affected males) are insensitive to androgens, resulting in a female-typical peripheral phenotype despite possession of inguinal testes that are androgen secretory. Androgen-dependent neural and behavioral processes may likewise show atypical sexual differentiation. Interestingly, these mutant rats display elevated serum corticosterone, suggesting a chronic anxiety phenotype and dysregulated hypothalamic-pituitary-adrenal axis. In order to understand if elevated anxiety-like behavior is a possible mediating variable affecting the display of certain androgen-dependent behaviors, we compared the performance of Tfm-affected males to wild type males and females in the elevated plus maze (EPM). Two well-established indicators of anxiety-like behavior in the EPM were analyzed: total percentage of time spent on the open arms, and the percentage of open arm entries. We also analyzed the total number of open arm entries. Interestingly, Tfm-affected males spent less percentage of time on the open arms than both males and females, suggesting increased anxiety-like behavior. Percentage of open arm entries and the total number of arm entries was comparable between the groups, indicating that the observed decrease in the percentage of time spent on the open arms was not due to a global reduction in exploratory behavior. These data, in contrast to earlier reports, thus implicate androgen receptor-mediated functions in the expression of anxiety behaviors in male rats. Given that anxiety is widely reported as a precipitating factor in depression, studying the role of the androgen receptor in anxiety may give insights into the pathogenesis of major depressive disorder.

Partner preference and mount latency are masculinized in androgen insensitive rats.

The sexual motivation of male rats may be inferred from a preference to stay in proximity to estrous female partners, and also from a short latency to show mounting behavior. Here, partner preference was assessed in rats carrying the testicular feminization mutation (TFM), and compared to wild type (WT) males in one version of this paradigm, and WT females and males in another version. Additionally, mount latency was quantified in the TFMs and compared to WT males in order to assess arousal levels, as this has not been previously reported. When presented with a choice between proximity to an estrous or non-estrous female, WT males and TFMs demonstrated similar preferences for the estrous female. Estrous females, conversely, preferred to spend time with the WT male. In agreement with previous reports we observed several sexual performance deficits in the TFMs, but mount latencies were in the male range. Given that the TFMs reliably choose to spend time with the estrous female in the partner preference tests, and that they display normal arousal levels (reflected in masculinized mount latencies), the data suggest the motivation to engage in sexual behavior is masculine in the TFM rat and that possession of functional androgen receptors is not crucial in these behaviors.

Analysis of Foxp2 expression in the cerebellum reveals a possible sex difference.

Deletion of the gene Foxp2 affects ultrasonic vocalizations and induces morphological abnormalities in the Purkinje cell layer of the cerebellum in mice. Castration decreases the production of ultrasonic vocalizations in rats, but the mechanisms of androgenic regulation of ultrasounds are unknown. We explored a possible relationship between Foxp2 expression and androgens in the Purkinje cell layer of wild-type and androgen-insensitive male rats, as well as estrous and nonestrous female rats. Analyses of relative optical densities of Foxp2 immunoreactivity revealed significantly greater immunolabeling in the wild-type and testicular feminization mutation-affected male rats (which did not differ from each other) than in either the estrous or nonestrous female rats (which similarly did not differ from each other). These data suggest a sex difference in Foxp2 expression in the cerebellum.