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Cesarean delivery is associated with diminished plasma levels of several 'birth-signaling' hormones, such as oxytocin and vasopressin. These same hormones have been previously shown to exert organizational effects when acting in early life. For example, our previous work found a broadly gregarious phenotype in prairie voles exposed to oxytocin at birth. Meanwhile, cesarean delivery has been previously associated with changes in social behavior and metabolic processes related to oxytocin and vasopressin. In the present study, we investigated the long-term neurodevelopmental consequences of cesarean delivery in prairie voles. After cross-fostering, vole pups delivered either via cesarean or vaginal delivery were studied throughout development. Cesarean-delivered pups responded to isolation differently in terms of their vocalizations (albeit in opposite directions in the two experiments), huddled in less cohesive groups under warmed conditions, and shed less heat. As young adults, we observed no differences in anxiety-like or alloparental behavior. However, in adulthood, cesarean-delivered voles of both sexes failed to form partner preferences with opposite sex conspecifics. In a follow-up study, we replicated this deficit in partner-preference formation among cesarean-delivered voles and were able to normalize pair-bonding behavior by treating cesarean-delivered vole pups with oxytocin (0.25 mg/kg) at delivery. Finally, we detected minor differences in regional oxytocin receptor expression within the brains of cesarean-delivered voles, as well as microbial composition of the gut. Gene expression changes in the gut epithelium indicated that cesarean-delivered male voles have altered gut development. These results speak to the possibility of unintended developmental consequences of cesarean delivery, which currently accounts for 32.9 % of deliveries in the U.S. and suggest that further research should be directed at whether hormone replacement at delivery influences behavioral outcomes in later life., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Repeated formation and subsequent dissolution of romantic relationships is common in humans across a lifetime. The socially monogamous prairie vole (Microtus ochrogaster) is used to study mechanisms of these bonds. At least in the laboratory, male prairie voles form bonds with a new female partner after loss of a previous partner. Initial bond formation depends on activation of dopamine D2-like receptors in the nucleus accumbens. Blocking activity of this receptor subtype disrupts formation of an animal's first pair bond. It is not known if these same D2-like receptors facilitate pair bonding with a subsequent partner after previous partner loss. This study examined the effects of D2-like receptor blockade on repeated pair bonding in male prairie voles. Males were paired with an initial female and allowed to mate before being separated. After a 5-day separation, males were then treated with either saline or eticlopride, a selective D2-receptor antagonist, prior to being paired with a second female and being allowed to mate. After a second separation, males were tested to determine if they developed a preference for spending time with their first or second mate. Eticlopride-treated males spent more time in a cage containing one of their previous partners compared to time in an empty cage but did not form a selective preference for either partner. Saline-treated males preferred their second, more recent partner. D2 receptor antagonism, then, disrupts bond formation in a second pairing but does not help to maintain a bond with the initial partner., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The prairie vole has proven a valuable animal model for the neurobiological study of social monogamy and pair bonding. Previous research has focused almost exclusively on virgin prairie voles forming pair-bonds for the first time - a paradigm with limited relevance to human social behavior. In the present study, we used stud males to assess the impact of repeated pair-bond formation and dissolution on the behaviors and neurobiology relevant to subsequent pair-bond formation. Stud males were tested for behavioral and neurobiological effects of repeated pair-bonding after the 1st, 5th, and 10th pairing. Aged breeder males that experienced minimal pair-bond dissolution were included to control for the effects of aging. Results showed that male prairie voles readily form new pair-bonds after repeated pair-bond dissolution. In terms of social monogamy, old age was associated with males spending less time in close social contact with unfamiliar females. There were no effects of age nor number of lifetime pairings on depressive-like behavior or paternal behavior toward pups. Within the brain, the patterns of oxytocin (OTR) and vasopressin type 1a (V1aR) receptors were largely unaffected, with the following exceptions: 1) males with only a single pairing had higher OTR densities in the paraventricular thalamus and bed nucleus of the stria terminalis; 2) there was an age-related increase in the density of OTR in the caudate putamen and an age-related decline in the density of V1aR in the cortical amygdala. The present findings have translational relevance to human social behavior in the context of aging and social experience., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The advancement of neuroscience depends on continued improvement in methods and models. Here, we present novel techniques for the use of awake functional magnetic resonance imaging (fMRI) in the prairie vole (Microtus ochrogaster) - an important step forward in minimally-invasive measurement of neural activity in a non-traditional animal model. Imaging neural responses in prairie voles, a species studied for its propensity to form strong and selective social bonds, is expected to greatly advance our mechanistic understanding of complex social and affective processes. The use of ultra-high-field fMRI allows for recording changes in region-specific activity throughout the entire brain simultaneously and with high temporal and spatial resolutions. By imaging neural responses in awake animals, with minimal invasiveness, we are able to avoid the confound of anesthesia, broaden the scope of possible stimuli, and potentially make use of repeated scans from the same animals. These methods are made possible by the development of an annotated and segmented 3D vole brain atlas and software for image analysis. The use of these methods in the prairie vole provides an opportunity to broaden neuroscientific investigation of behavior via a comparative approach, which highlights the ethological relevance of pro-social behaviors shared between voles and humans, such as communal breeding, selective social bonds, social buffering of stress, and caregiving behaviors. Results using these methods show that fMRI in the prairie vole is capable of yielding robust blood oxygen level dependent (BOLD) signal changes in response to hypercapnic challenge (inhaled 5% CO2), region-specific physical challenge (unilateral whisker stimulation), and presentation of a set of novel odors. Complementary analyses of repeated restraint sessions in the imaging hardware suggest that voles do not require acclimation to this procedure. Taken together, awake vole fMRI represents a new arena of neurobiological study outside the realm of traditional rodent models., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The long-term effects of developmental experiences on social behavior, and the neuropeptide systems such as oxytocin which subserve the behavior, are still little understood. In this article, we review various types of early experience, including normal development, knockout models, pharmacological exposures, and early social experiences. We consider the processes by which experience can affect oxytocin receptor binding, and what is known about the directionality of experience effects on oxytocin receptors. Finally, we attempt to synthesize the literature into a predictive model as to the direction of early experience effects on oxytocin receptor binding potential, and whether these changes have functional significance. These predictions are relevant to current human health practice, given proposals to use chronic intranasal oxytocin to treat developmental disorders including autism and schizophrenia. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior., (Copyright © 2011 Elsevier Inc. All rights reserved.)