Neonatal exposure to endocrine active compounds or an ERbeta agonist increases adult anxiety and aggression in gonadally intact male rats.
ABSTRACT Endocrine active compounds (EACs) have been shown to influence a number of reproductive endpoints but less is known about how they might affect other hormone dependent behaviors including anxiety and aggression. Recent evidence suggests that these effects may be mediated through the beta form of the estrogen receptor (ERbeta). Using male Long Evans rats, we sought to determine how neonatal exposure to EACs affects anxiety and aggression in adulthood. Anxiety was assessed using the elevated plus maze and aggression was assessed 8 weeks later using the resident intruder test. To gain insight into which ER subtype (ERalpha vs ERbeta) might be mediating these effects we used agonists specific for ERalpha (1,3,5-tris(4-Hydroxyphenyl)-4-propyl-1H-pyrazole (PPT)) or ERbeta (Diarylpropionitrile (DPN)) as additional treatment groups. For these experiments the synthetic EAC bisphenol-A (BPA) and the phytoestrogen metabolite equol (EQ) were used. Male neonates were injected with either 0.05 ml sesame oil (control), 50 microg estradiol benzoate (EB), 1 mg/kg DPN, 1 mg/kg PPT, 50 microg/kg BPA, or 10 mg/kg EQ daily for 4 days beginning on the day of birth (PND 0). Compared to the oil treated controls, significantly fewer open arm entries were made by the males neonatally treated with DPN, EQ, or BPA. The DPN and EQ treated males were also more aggressive compared to the controls. These findings suggest that neonatal exposure to EACs with agonistic activity on ERbeta may influence affective behavior in adulthood, including anxiety and aggression.
Article: Estrogen receptor-alpha in the bed nucleus of the stria terminalis regulates social affiliation in male prairie voles (Microtus ochrogaster).[show abstract] [hide abstract]
ABSTRACT: Estrogen receptor alpha (ERalpha) typically masculinizes male behavior, while low levels of ERalpha in the medial amygdala (MeA) and the bed nucleus of the stria terminalis (BST) are associated with high levels of male prosocial behavior. In the males of the highly social prairie vole (Microtus ochrogaster), increasing ERalpha in the MeA inhibited the expression of spontaneous alloparental behavior and produced a preference for novel females. To test for the effects of increased ERalpha in the BST, a viral vector was used to enhance ERalpha expression in the BST of adult male prairie voles. Following treatment, adult males were tested for alloparental behavior with 1-3-day-old pups, and for heterosexual social preference and affiliation. Treatment did not affect alloparental behavior as 73% of ERalpha-BST males and 62.5% of control males were alloparental. Increasing ERalpha in the BST affected heterosexual affiliation, with ERalpha-BST males spending significantly less total time in side-by-side contact with females relative to time spent with control males. ERalpha-BST males did not show a preference for either the familiar or novel female. These findings differed significantly from those reported in ERalpha-MeA enhanced males, where ERalpha inhibited alloparental behavior and produced a preference for a novel female. The findings from this study suggest two things: first, that increased ERalpha in the BST decreases social affiliation and second, that altering ERalpha in different regions of the social neural circuit differentially impacts the expression of social behavior.PLoS ONE 01/2010; 5(1):e8931. · 4.09 Impact Factor