Project Summary/Abstract
Psychological stress can induce activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing the
function of multiple biological systems and posing a risk to mental and physical health. In contrast, positive
social interactions, especially social support from deeply rooted social bonds, can ameliorate stress-induced
mental, physiological, and behavioral deficits and improve an individual's overall well-being—a phenomenon
known as social buffering [1, 2]. Such social buffering effects have been described in both human [3-5] and
animal models [6, 7]. Although we have begun to understand the neuromechanisms underlying biobehavioral
responses to psychological stress, little is known about the neuromechanisms by which social support buffers
the stress response [1]. This is largely due to the difficulties inherent in studying neurobiological mechanisms in
humans as well as a lack of appropriate animal models to assess the effects of social buffering. Recently, the
socially monogamous prairie vole (Microtus ochrogaster) has emerged as an animal model to study the
neurobiology of social behavior. In prairie voles, mating induces pair bonding, which is regulated by several
neurochemicals including oxytocin (OT), vasopressin (AVP), corticotrophin releasing hormone (CRH), and
gamma-aminobutyric acid (GABA) [8, 9]. Pair bonding reduces stress-induced anxiety-like behavior by
attenuating the action of the HPA axis [10]. Interactions with the partner also promote the release of central OT
[11], which plays a role in attenuating the biobehavioral response to stress in female voles [12]. Using this
unique animal model, we propose, in Specific Aim 1, to examine how social buffering by a sibling cage mate or
a bonding partner attenuates immobilization (IMO)-induced stress responses in male and female prairie voles.
We will examine the effects of social buffering on (1) anxiety-like, depression-like, and affiliative behaviors,
(2) circulating levels of corticosterone (CORT), (3) CRH, OT, AVP, GABA, and their receptors gene and
protein expression in the paraventricular nucleus of the hypothalamus (PVN), and (4) neurochemical release in
the PVN during IMO and social buffering. In Specific Aim 2, we will perform pharmacological manipulations
with behavioral testing to examine the functional role of PVN OT, and its interactions with GABA, CRH and
AVP, in the social buffering of the stress response. In Specific Aim 3, we will examine the neurochemical and
physiological involvement of PVN neuromicrocircuitry in the regulation of social buffering. Data from this
study will not only enhance our understanding of sex differences in the neurochemical regulation of social
buffering of stress responses but also further establish a much needed animal model for such investigation.