Watson, Neil V.

The chapter, "Spatial memory performance in androgen insensitive male rats" was written by the listed authors including Bryan A. Jones (Douglas College Faculty). A collection of foundational texts on the nature and behavioral consequences of sex differences in the brain, allowing readers to follow the development of a rapidly growing but contentious field and giving them the tools to analyze emerging scientific findings from many perspectives. --From publisher description.

Perinatal administration of the endocrine disruptor bisphenol A (BPA) reportedly inhibits the sexual behavior of sexually naïve adult male rats. In order to evaluate the effects of BPA administration during early development on later reproductive behavior, we administered one of five doses of bisphenol A daily to pregnant female rats throughout gestation and lactation, and quantified the appetitive and consummatory sexual behaviors of the resultant male and female offspring over multiple sexual encounters in adulthood. Males receiving low dose perinatal BPA (50 μg/kg bw/day) showed persistent deficits in sexual behavior in adulthood. Males receiving the highest dose (5 mg/kg bw/day), however, were indistinguishable from controls with respect to consummatory sexual behaviors but showed decreased latencies to engage in those behaviors when sexually naïve, with significant non-linear, or U-shaped, dose–response relationships observed on the first and last day of testing. Adult female sexual behavior was not affected by early BPA administration at any dose tested. These results are consistent with previous reports that BPA exerts behavioral effects especially at low doses, and further indicates that BPA can cause lasting impairment of sexual behavior in males, but does not alter the normal development of female appetitive or consummatory sexual behaviors. To our knowledge, this is the first report indicating that adult sexual performance is impaired in sexually experienced animals following perinatal exposure to bisphenol A.

Bisphenol A (BPA) is an endocrine disrupting agent that can alter the normal gonadal steroid-sensitive sexual differentiation of the brain and behavior. While reproductive behavior and physiology are known to be altered by perinatal exposure to this compound, less is known about BPA's effects on sex differences in learning and measures of affect. In order to evaluate the effects of perinatal BPA treatment on learning and affect in adulthood, we exposed rats to one of five doses of BPA through gestation and lactation then examined adult behavior in the Morris Water Maze (MWM), the Elevated Plus Maze (EPM) and the Forced Swim Test (FST). No effect of BPA was observed in the MWM, but on both the EPM and FST, low doses (5 μg/kg) of BPA eliminated sex differences found between controls; furthermore, a non-monotonic dose–response observed in previous studies was confirmed for these tasks. Overall, our study adds to the growing data suggesting that BPA interferes with the normal development of affective behaviors in a non-linear, dose-dependent manner.

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.

The industrial plasticizer bisphenol A (BPA) is a ubiquitous endocrine disruptor to which the general human population is routinely exposed. Although BPA is well known as an estrogenic mimic, there have been some suggestions that this compound may also alter activity at the androgen receptor. To determine whether BPA does have antiandrogenic properties, we evaluated BPA effects in the spinal nucleus of the bulbocavernosus and dorsolateral nucleus, sexually dimorphic groups of motor neurons in the lumbar spinal cord that are critically dependent on androgens for survival and maintenance, as well as the monomorphic retrodorsolateral nucleus. In experiment 1, we administered varying concentrations of BPA to juvenile rats pre- and postnatally and examined both the number and size of motor neurons in adulthood. In experiment 2, different doses of BPA were given to adult rats for 28 days, after which the soma size of motor neurons were measured. Although no effect of BPA on neural survival or soma size was noted after perinatal BPA exposure, BPA exposure did result in a decrease in soma size in all motor neuron pools after chronic exposure in adulthood. These findings are discussed with regard to putative antiandrogenic effects of BPA; we argue that BPA is not antiandrogenic but is acting through nonandrogen receptor-dependent mechanisms. Part of the " Special Series: Endocrine Society Centennial Celebration".