Early Life Adversity and Adult Social Behavior: Focus on Arginine Vasopressin and Oxytocin as Potential Mediators

Abstract

Exposure to stress during the early postnatal period (i.e., early life stress, ES) can impact brain physiology and modify individual variability in adult social behavior. Arginine vasopressin (AVP) and oxytocin (OXT) are two centrally released neuropeptides that are involved in shaping essential social behaviors, like aggression, social recognition, and social motivation. AVP and OXT modulate activity in brain regions important for the establishment of social behavior, and may be particularly sensitive to ES. In this review, we discuss whether ES alters the characteristics of the AVP- and OXT- systems in rodents, and whether these changes are associated with later alterations in aggression, social recognition, and social motivation. We have integrated causal studies indicating that (1) ES affects AVP/OXT, and (2) that changing AVP/OXT in affected regions alters social behavior. Although there is encouraging evidence that ES causes AVP- and OXT-system changes, and that these may mediate social behavior, a comprehensive understanding of the exact nature of AVP- and OXT changes and whether they are causal in establishing these behavioral disturbances needs further investigation. As there are indications that ES alters AVP- and OXT characteristics in humans as well, and that these may interact with adult predisposition to psychopathology with social dysfunction, future rodent studies may lay ground for a better understanding of such changes in humans. Ultimately, this may assist in developing therapeutic strategies to target ES effects on social behavior.

Birth signalling hormones and the developmental consequences of caesarean delivery

“…Specifically, effects of early‐life stress include changes in reactivity of the hypothalamic‐pituitary‐adrenal (HPA) axis, which lead to heightened stress susceptibility in later life 32,162 ; changes in the brain regions which regulate the HPA‐axis via negative‐feedback, such as the amygdala, hippocampus and prefrontal cortex 32 ; neuroimmunological changes 163 ; changes in respiratory functioning 164 ; and an increased risk for developing neurodevelopmental disorders, 34 obesity 165‐168 and cardiovascular disease 169 . There is also substantial neuroendocrine cross‐talk, such that the effects of early‐life stress manifest as changes in OXT and AVP as seen in both human 170 and rodent studies 137,171 …”

“…Based on their shared neuroendocrine mechanisms, we may find new domains affected by CS delivery. One of the most well‐studied consequences of early‐life stress is that of disruptions to social behaviour 171 . In rodents, early‐life stress disrupts attachment, as seen in infant rats 273 .…”

The HPA Axis under Stress and Aging: Individual Vulnerability is Associated with Behavioral Patterns and Exposure Time

“…Indeed, a number of reports indicate a relationship of individual behavior under stress to various physiological processes, for example, with the activity level of antioxidant enzymes and the intensity of free radical processes, [ 9,53 ] function of the pancreatic islet, [ 54 ] endocrine functions in the gastrointestinal tract, [ 55 ] and the activity of the neuro‐hypophysial system. [ 56,57 ] There is particularly considerable data on the relationship of behavior to HPA axis function. [ 3,7,9,12,16–19 ]…”

Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice

“…To understand how ELS alters neurobiology in a way that promotes such aberrant behavior, many studies have used rodent models of maternal separation in which early postnatal pups are deprived of necessary maternal care by separating them from the dam for extended periods of time (for reviews see Nishi, Horii-Hayashi, & Sasagawa, 2014;Orso et al, 2019;Tractenberg et al, 2016). Rodent maternal separation during the early postnatal period has been shown to produce an array of adolescent and adulthood behavioral effects not limited to increased anxiety-like behavior (Caldji, Diorio, & Meaney, 2000;Daniels, Pietersen, Carstens, & Stein, 2004;Lee et al, 2007;Levine, 1967;Liu, Diorio, Day, Francis, & Meaney, 2000;Matthews, Hall, Wilkinson, & Robbins, 1996), hyper-responsiveness to stressors (Holmes et al, 2005;Meaney, 2001;Ogawa et al, 1994;Plotsky & Meaney, 1993), altered reward learning and cognition (Forster, Anderson, Scholl, Lukkes, & Watt, 2018;Liu et al, 2000;Matthews & Robbins, 2003;Portero-Tresserra et al, 2018;Pryce, Bettschen, Nanz-Bahr, & Feldon, 2003;Sasagawa et al, 2017), deviations in normal fear learning and memory (Callaghan, Graham, Li, & Richardson, 2013;Chocyk et al, 2014), and deficits in social behavior (Frank et al, 2019;Kompier, Keysers, Gazzola, Lucassen, & Krugers, 2019;Venerosi, Cirulli, Capone, & Alleva, 2003;Wang et al, 2017).…”

“…For example, ELS increases corticotropin-releasing factor (CRF) expression in several neural regions (Ladd, Owens, & Nemeroff, 1996;Plotsky & Meaney, 1993;Plotsky et al, 2005), elicits adulthood stressor-induced hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis (Holmes et al, 2005;Ladd et al, 2000;Ogawa et al, 1994;Plotsky & Meaney, 1993;Rosenfeld, Suchecki, & Levine, 1992), and alters serotonergic transmission and oscillatory signaling in regions such as the hippocampus and cortex (Lee et al, 2007;Matthews, Dalley, Matthews, Tsai, & Robbins, 2001;Murthy et al, 2019;Vazquez, Lopez, Van Hoers, Watson, & Levine, 2000). ELS deficits specific to social behaviors may be due to altered neural transmission involving CRF (Gutman & Nemeroff, 2003;Plotsky et al, 2005), monoamine signaling, or peptides such as oxytocin (OT) and arginine vasopressin (AVP; Kompier et al, 2019).…”