Joint contributions of affiliative social contact, stress in adolescence and oxytocin to fear behaviour in adult rats

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Fear is perhaps our most primal emotion. Appropriate levels of fear yield adaptive defensive responses that promote survival. Excessive fear reactions can be maladaptive. I am interested in the neural regulation of fear expression and how this process is shaped by prior experience. Experiencing stress in infancy and/or early childhood can, in certain instances, enhance (rather than impede) resilience in later life. I want to know if experience-induced increases in resilience can also be initiated in adolescence. Our recent findings suggest that access to affiliative social contact might shift the lasting outcomes of adolescent stress toward enhanced resilience, as evidenced by lower levels of fear expression in adulthood. We now want to extend those findings. We will expose single and pair-housed, male and female rats to intermittent physical stress (IPS) in early or mid-adolescence and then test their behavioural responses to acute threats in adulthood. We expect that pair-housed rats with a history of IPS in adolescence will display lower levels of behavioural fearfulness relative to no-stress/pair-housed control rats, whereas the reverse will be found in single-housed/IPS rats. Additional experiments will explore the potential involvement of the neuropeptide, oxytocin (OT) in experience-induced resilience. This involves processing rats through our adolescent stress protocol (as described above) and then labelling their adult brain tissue with a marker for OT. We expect that pair-housed/IPS rats will display the highest number of OT positive cells in hypothalamic areas rich in OT-producing cells. These same rats will also display the highest density of OT positive fibers in two interconnected brain regions implicated in defensive behaviour, the lateral septum (LS) and anterior hypothalamus (AHA). To further explore the involvement of OT in fear reduction, we will expose single and pair-housed rats with a history of IPS in adolescence to an acute threat, the shock-probe burying test (SPBT) in adulthood. After the SPBT, we will evaluate threat-induced activation of OT-producing cells by processing their brain tissue for double immuno-labelling using antibodies for the neuronal activity marker, cFos and OT. We expect that pair-housed/IPS rats will display the lowest levels of fear expression in the SPBT, and this will be associated with the highest number of double labelled cells in the hypothalamus. A complimentary series of experiments aims to determine whether infusing OT directly into the LS or AHA reduces rats' fear expression in various behavioural tests. This research will provide novel information about factors (affiliative social contact, age at adversity, sex, oxytocin) that potentially interact to shape the lasting outcomes of adversity in adolescence, thus conferring either greater sensitivity or resilience to adverse events in later life. Ultimately, the findings might inform endeavors aimed at supporting vulnerable youth in Canada.