Abstract

Investigations addressing addiction and social behaviour have found differences between males and females (men and women). Early life exposure to antibiotics (ELEA) induces addiction?like behaviours in adult male Sprague–Dawley (SD) rats, but not in females, while changing dopamine neurochemistry in females but not in males (doi: 10.3389/fphar.2022.837652). Female oestrogen regulates brain dopamine levels and release, while oestrogen circulation is influenced by gut microbes through intestinal ?-glucuronidase activity, which further contributes to oestrogen's impact on the brain. Since the dopaminergic system is an important regulator of social behaviour and its function is affected by oestradiol concentrations, we asked whether ELEA impacts these behaviours later in life and if changes in intestinal gut ?-glucuronidase activity relate to these changes. ELEA was achieved by oral administration of bacitracin, neomycin, vancomycin (100 mg/kg each) and pimaricin (5 ?g/kg) to pregnant SD dams from embryonic Day 18 to postnatal day (PND) 7. Vehicle-treated pregnant SD dams served as controls. Behavioural analysis was conducted on male and female offspring from PND 35–37. Half of the subjects underwent gonadectomy (GDX) to remove the influence of sex steroids. ELEA prevented weight loss associated with behavioural testing in males. Three-way ANOVA revealed a main effect of ELEA, reducing pinning, pouncing, total time of social play and social grooming. In GDX males, ELEA diminished social interaction in the presence of an unknown rat. ?-glucuronidasee activity was reduced in females by ELEA and GDX. ELEA reduces some social behaviours in a sex-independent manner, while sex-dependently lowering intestinal beta-glucuronidase activity, suggesting that early-life gut symbiont acquisition influences social coping strategies and intestinal oestradiol metabolism later in life. (Figure presented.). © 2025 International Society for Neurochemistry.