Oxytocin: who needs it?

The neuropeptide oxytocin has been implicated in the initiation of maternal behavior, based on studies in rats and sheep. Females in both of these species naturally avoid infants until parturition when they begin to show an intense interest in maternal care. Oxytocin pathways in the brain appear to be important for this transition from avoidance to approach of the young. Recent studies in mice with a null mutation of the oxytocin gene suggest a different scenario. These mice, which completely lack oxytocin, exhibit full maternal and reproductive behavior, except for a deficit in milk ejection. Apparently, oxytocin is not essential for maternal behavior in this species. Consistent with the role of oxytocin for the transition from avoidance to approach in rats and sheep, nulliparous mice show full maternal behavior and therefore do not require the peptide for the initiation of maternal care. The species differences in the behavioral effects of oxytocin are associated with profound species differences in the location of oxytocin receptors in the brain. Recent transgenic studies suggest that these species differences in the neuroanatomical distribution of oxytocin receptors may be a function of inter-species variation in the flanking region of the oxytocin receptor gene. So, who needs oxytocin? For maternal care, not mice and (possibly) other species, like primates, with promiscuous parental care. Most important, in considering the behavioral or cognitive functions of oxytocin, one cannot accurately extrapolate across species unless one knows the species have the same neuroanatomical location of oxytocin receptors.

Cellular mechanisms of social attachment.

Pharmacological studies in prairie voles have suggested that the neuropeptides oxytocin and vasopressin play important roles in behaviors associated with monogamy, including affiliation, paternal care, and pair bonding. Our laboratory has investigated the cellular and neuroendocrine mechanisms by which these peptides influence affiliative behavior and social attachment in prairie voles. Monogamous prairie voles have a higher density of oxytocin receptors in the nucleus accumbens than do nonmonogamous vole species; blockade of these receptors by site-specific injection of antagonist in the female prairie vole prevents partner preference formation. Prairie voles also have a higher density of vasopressin receptors in the ventral pallidal area, which is the major output of the nucleus accumbens, than montane voles. Both the nucleus accumbens and ventral pallidum are key relay nuclei in the brain circuits implicated in reward, such as the mesolimbic dopamine and opioid systems. Therefore, we hypothesize that oxytocin and vasopressin may be facilitating affiliation and social attachment in monogamous species by modulating these reward pathways.

Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtus ochrogaster).

The prairie vole (Microtus ochrogaster), a monogamous rodent that forms long-lasting pair bonds, has proven useful for the neurobiological study of social attachment. In the laboratory, pair bonds can be assessed by testing for a partner preference, a choice test in which pair-bonded voles regularly prefer their partner to a conspecific stranger. Studies reported here investigate the role of dopamine D2-like receptors (i.e., D2, D3, and D4 receptors) in the nucleus accumbens (NAcc) for the formation of a partner preference in female voles. Mating facilitated partner preference formation and associated with an approximately 50% increase in extracellular dopamine in the NAcc. Microinjection of the D2 antagonist eticlopride into the NAcc (but not the prelimbic cortex) blocked the formation of a partner preference in mating voles, whereas the D2 agonist quinpirole facilitated formation of a partner preference in the absence of mating. Taken together, these results suggest that D2-like receptors in the NAcc are important for the mediation of social attachments in female voles.

Dopamine D2 receptor-mediated regulation of partner preferences in female prairie voles (Microtus ochrogaster): a mechanism for pair bonding?

This study examined the role of dopamine (DA) in partner preference (PP) formation in female prairie voles (Microtus ochrogaster). The nonspecific DA antagonist haloperidol blocked mating-induced PP, whereas the nonspecific DA agonist apomorphine induced PP without mating. The D2 antagonist eticlopride, but not the D1 antagonist SCH23390, blocked PP, whereas the D2 agonist quinpirole, but not the D1 agonist SKF38393, induced PP without mating. Injections of eticlopride before or immediately after mating, but not 24 hr after mating, impaired PP, indicating that DA's effects were not due to an interference with mating or sensory recognition. Finally, intracerebroventricular injections of eticlopride diminished PP. Together, these data suggest that mating-induced PP requires activation of D2 receptors and that social experience may activate dopaminergic pathways, with enduring effects on behavior.

The actor as context for social judgments: effects of prior impressions and stereotypes.

Three experiments identified conditions under which trait judgments made about a behavior were more likely to influence later judgments of the behavior. In Experiment 1, participants made trait judgments about numerous behaviors presented with photos of actors. Some behaviors were repeated, paired with the same or a different actor. All repeated behaviors were judged faster than new behaviors. Facilitation was greatest when repeated behaviors were paired with the same actor, suggesting greater influence of prior judgments in this condition. Experiments 2 and 3 replicated this effect, and the pattern of response times (RTs) suggested a stronger association between the actor and behavior when a prior impression of the actor had been formed (Experiment 2) and when the behavior was stereotypic of the actor's group (Experiment 3). Level of prejudice moderated RT patterns in Experiment 3. Implications for context effects, the nature of trait inferences, and stereotype change are discussed.

Gene targeting approaches to neuroendocrinology: oxytocin, maternal behavior, and affiliation.

Transgenic technology affords exciting new opportunities in the field of behavioral neuroendocrinology. We have extended our research into the behavioral function of oxytocin in maternal and social behavior using two transgenic approaches: (i) targeted deletion of the oxytocin gene in mice and (ii) augmented oxytocin receptor expression in the brain. Mice genetically deficient in oxytocin can mate, give birth, and display normal maternal behavior; however, milk ejection and certain aspects of social behavior are affected. Comparative studies of oxytocin receptors have led to the observation that species differences in social organization are associated with differences in receptor distribution. Specifically, monogamous prairie voles and nonmonogamous, asocial montane voles exhibit different patterns of OT receptor expression in the brain. Transgenic mice have been created with a reporter gene driven by the prairie vole oxytocin receptor gene promoter. Analysis of the expression pattern suggests that it should be possible to manipulate receptor expression in the vole brain in order to examine the effects of receptor distribution on behavior.