Consolation behavior toward distressed others is common in humans and great apes, yet our ability to explore the biological mechanisms underlying this behavior is limited by its apparent absence in laboratory animals. Here, we provide empirical evidence that a rodent species, the highly social and monogamous prairie vole (Microtus ochrogaster), greatly increases partner-directed grooming toward familiar conspecifics (but not strangers) that have experienced an unobserved stressor, providing social buffering. Prairie voles also match the fear response, anxiety-related behaviors, and corticosterone increase of the stressed cagemate, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused into this region abolishes the partner-directed response, showing conserved neural mechanisms between prairie vole and human.

Rationale Love has long been referred to as an addiction in literature and poetry. Scientists have often made comparisons between social attachment processes and drug addiction, and it has been suggested that the two may share a common neurobiological mechanism. Brain systems that evolved to govern attachments between parents and children, and between monogamous partners, may be the targets of drugs of abuse and serve as the basis for addiction processes. Objectives Here, we review research on drug addiction in parallel with research on social attachments, including parent-offspring attachments and social bonds between mating partners. This review focuses on the brain regions and neurochemicals with the greatest overlap between addiction and attachment, and in particular the mesolimbic dopamine pathway. Results Significant overlap exists between these two behavioral processes. In addition to conceptual overlap in symptomatology, there is a strong commonality between the two domains regarding the roles and sites of action of dopamine, opioids, and corticotrophin-releasing factor (CRF). The neuropeptides oxytocin and vasopressin are hypothesized to integrate social information into attachment processes that is not present in drug addiction. Conclusions Social attachment may be understood as a behavioral addiction, whereby the subject becomes addicted to another individual and the cues that predict social reward. Understandings from both fields may enlighten future research on addiction and attachment processes.

Despite significant evidence that opioids are involved in attachment by mediating social reward and motivation, the role of opioids in the formation of adult social attachments has not been explored. We used the socially monogamous prairie vole (Microtus ochrogaster) to explore the role of endogenous opioids in social bonding by examining partner preference formation in female prairie voles. We hypothesized that m-opioid receptors (MORs) in the striatum have a critical role in partner preference formation. We therefore predicted that peripheral administration of an opioid receptor antagonist would inhibit partner preference formation, and more specifically, that m-opioid selective receptor blockade within the striatum would inhibit partner preference formation. To test our hypotheses, we first administered the non-selective opioid antagonist naltrexone peripherally to females during an 18-h cohabitation with a male and later tested the female with a partner preference test (PPT). Females showed a dose schedule-dependent decrease in partner preference in the PPT, with females in the continuous dose group displaying stranger preferences. Next, we administered microinjections of the MOR selective antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) into either the nucleus accumbens shell (NAS) or the caudate-putamen (CP) immediately before a 24-h cohabitation with a male, and later tested the female with a PPT. Females receiving CTAP into the CP, but not the NAS, showed no preference in the PPT, indicating an inhibition of partner preference formation. We show here for the first time that MORs modulate partner preference formation in female prairie voles by acting in the CP.

The partner preference test (PPT) is commonly used to examine sexual and social preferences in rodents. The test offers experimental subjects a choice between two stimulus animals, and time spent with each is used to calculate a preference score. In monogamous prairie voles (Microtus ochrogaster), the PPT has been paramount to the study of pair bonding. Although powerful, use of the PPT in voles has depended primarily on human manual scoring. Manual scoring is timeconsuming and is susceptible to bias and fatigue, limiting the use of the PPT in high-throughput studies. Here we compared manual scoring (real-time and 16x) and two automated scoring metrics: "social proximity" and "immobile social proximity" We hypothesized that "immobile social contact" would provide data most comparable to manually scored "huddling", and thus be the most sensitive measure of partner preference in prairie voles. Each automated metric produced data that highly correlated with manual scoring (R > 0.90); however, "immobile social contact" more closely reflected manually scored huddling (R = 0.99; P < 0.001). "Social proximity" and "immobile social contact" were then used to detect group partner preferences in four data sets that varied by cohabitation length and sex. "Immobile social contact" revealed a significant partner preference in each data set; "social proximity" detected partner preferences in only three of the four. Our results demonstrate the utility of automated systems in high-throughput PPTs, and further confirm that automated systems capable of scoring "immobile social contact" yield results indistinguishable from manual scoring.

Vesicular monoamine transporter 2 (VMAT2, SLC18A2) is a transmembrane transporter protein that packages dopamine, serotonin, norepinephrine, and histamine into vesicles in preparation for neurotransmitter release from the presynaptic neuron. VMAT2 function and related vesicle dynamics have been linked to susceptibility to oxidative stress, exogenous toxicants, and Parkinson’s disease. To address a recent depletion of commonly used antibodies to VMAT2, we generated and characterized a novel rabbit polyclonal antibody generated against a 19 amino acid epitope corresponding to an antigenic sequence within the C-terminal tail of mouse VMAT2. We used genetic models of altered VMAT2 expression to demonstrate that the antibody specifically recognizes VMAT2 and localizes to synaptic vesicles. Furthermore, immunohistochemical labeling using this VMAT2 antibody produces immunoreactivity that is consistent with expected VMAT2 regional distribution. We show the distribution of VMAT2 in monoaminergic brain regions of mouse brain, notably the midbrain, striatum, olfactory tubercle, dopaminergic paraventricular nuclei, tuberomammillary nucleus, raphe nucleus, and locus coeruleus. Normal neurotransmitter vesicle dynamics are critical for proper health and functioning of the nervous system, and this well-characterized VMAT2 antibody will be a useful tool in studying neurodegenerative and neuropsychiatric conditions characterized by vesicular dysfunction.