The consumption of alcohol during pregnancy is frequent despite clear guidelines that indicate that abstinence is the safest option to prevent adverse offspring outcomes. These outcomes range from overt craniofacial abnormalities through to outcomes such as mental illness, hyperactivity and social difficulties. Human and animal studies have demonstrated that these neurological outcomes may be due to impaired function of the hypothalamic-pituitary-adrenal axis (HPA) in offspring, resulting in altered basal glucocorticoid tone and disrupted responsiveness to stress. However, little is known of the impact of alcohol consumption around the time of conception, known as the periconceptional period, on offspring HPA function. Therefore, this study aimed to use a well-established rat model of ethanol consumption during the periconceptional period (PC:EtOH) to investigate offspring HPA activity, including behaviours, stress responsiveness and underlying molecular pathways. As alcohol consumption directly alters HPA function, this study also aimed to examine if PC:EtOH exposure impairs maternal HPA activity and related physiological pathways, including renal and metabolic function. Female Sprague-Dawley rats were treated with PC:EtOH (12.5% v/v EtOH liquid diet) or a control diet from 4 days before conception, until embryonic day (E) 4. Behavioural tests were performed on offspring at three months of age to assess mental illness-like phenotypes (utilising the Forced Swim Test [FST] and Social Interaction [SI] paradigm), and at five months of age, HPA reactivity tests (combined dexamethasone suppression test [DST] and corticotropin-releasing hormone stimulation test [CST] and restraint stress) were performed. In a separate study, basal corticosterone concentrations were measured at 6 months, and adrenal glands were collected for analysis of steroidogenic gene expression. Aged cohorts (12-14 months) were utilised to measure basal plasma corticosterone, followed by the collection of adrenal glands, pituitary glands, hypothalamus and hippocampal tissue for analysis of various steroidogenesis and glucocorticoid signalling genes and pathology. In a separate cohort of aged rats, telemetry was used to asses blood pressure, heart rate and plasma corticosterone concentrations during 30-minute restraint stress. Maternal hormones (corticosterone, aldosterone), renal function and plasma glucose and lipids were assessed at various stages in gestation. Adrenal glands were collected from dams at E5, E15 and E20 for analysis of steroidogenic gene expression. Placental samples were collected at E20 and genes expression of the glucocorticoid (Nr3c1) and corticotrophin hormone receptor (Crh-r1) measured. 3 | P a g e This study revealed that PC:EtOH exposure resulted in altered offspring behavioural outcomes, including increased depressive-like behaviour in the forced swim test and altered social interaction with a novel rat. Adult offspring also demonstrated HPA hyperactivity, with elevated responses to the DST/CST challenge. Although there w...