Evaluation of oxytocin as a possible treatment for the effects of prenatal alcohol exposure on neurogenesis, stress reactivity, and anxiety-like behaviour in male and female rats

The hippocampus provides inhibitory regulation on the hypothalamic-pituitary-adrenal (HPA) axis. Hippocampal neurogenesis (birth of new neurons) has been implicated in the HPA axis ability to mount an appropriate response to stress. Both the hippocampus and HPA axis are highly susceptible to early environmental modulation. Prenatal alcohol exposure (PAE) has been shown to alter HPA axis activity, reduce hippocampal neurogenesis, and increase anxiety-like behaviour. Dysregulated HPA axis activity and altered hippocampal neurogenesis following PAE likely underlie the behavioural expression of anxiety. The neuropeptide, oxytocin (OT), has been shown to dampen HPA axis response to stress, stimulate hippocampal neurogenesis, and act as an anxiolytic. OT is a prime therapeutic candidate to treat the altered stress responsivity and increased anxiety following PAE because it may act on underlying neurogenic and endocrine mechanisms. The objective of this study was to examine whether OT can modulate the effects of PAE on neurogenic, stress-response, and behavioural outcomes. In adulthood, male and female offspring from alcohol-fed, pair-fed, and control dams were treated daily with OT or vehicle for 10 days. OT-treated animals exhibited sedative-like effects and reduced locomotor activity. PAE animals showed fewer sedative-like effects, which may suggest altered OT sensitivity, as well as exhibited hyperactivity. Decreased locomotor activity following OT may preferentially impact hyperactive PAE animals. Interestingly, PAE animals also showed decreased anxiety-like behaviour; however, this effect may be confounded by hyperactivity and reflect impulsivity or inappropriate risk-assessment. PAE males showed attenuated CORT recovery following acute restraint stress, which OT did not modulate. PAE animals exhibited increased density of immature neurons in the dorsal dentate gyrus, whereas OT had no effect on neurogenesis. Utilizing the methods in this study OT was not able to mitigate the effects of PAE on endocrine or neurogenic domains. However, OT may act to reduce hyperactivity following PAE, which may support attenuation of learning and memory deficits, attention problems, and impulsivity. Our findings are an important extension of previous work on altered neurogenic, endocrine, and behavioural responses following PAE. Our results support and extend literature on the use of OT as a therapeutic intervention, with novel utilization following PAE.Medicine, Faculty ofGraduat