Oxytocin and the oxytocin receptor underlie intrastrain, but not interstrain, social recognition

Abstract

We studied three lines of oxytocin (Oxt) and oxytocin receptor (Oxtr) knockout (KO) male mice (Oxt−/−, total Oxtr−/−, and partial-forebrain Oxtr (OxtrFB/FB)) with established deficits in social recognition to further refine our understanding of their deficits with regard to stimulus female's strain. We used a modified social discrimination paradigm in which subjects are singly housed only for the duration of the test. Additionally, stimulus females are singly-housed throughout testing and are presented within corrals for rapid comparison of investigation by subject males. Wildtype (WT) males from all three lines discriminated between familiar and novel females of three different strains (C57BL/6, Balb/c, Swiss-Webster). No KO males discriminated between familiar and novel Balb/c or C57BL/6 females. Male Oxt−/− and Oxtr−/− mice, but not OxtrFB/FB mice, discriminated between familiar and novel Swiss-Webster females. As this might indicate a global deficit in individual recognition for OxtrFB/FB males, we examined their ability to discriminate between females from different strains and compared performance with Oxtr−/− males. WT and KO males from both lines were able to distinguish between familiar and novel females from different strains, indicating the social recognition deficit is not universal. Instead, we hypothesize that the Oxtr is involved in “fine” intra-strain recognition, but is less important in “broad” inter-strain recognition. We also present the novel finding of decreased investigation across tests, which is likely an artifact of repeated testing and not due to stimulus female's strain or age of subject males.

Oxytocin differentially modulates compromise and competitive approach but not withdrawal to antagonists from own vs. rivaling other groups

“…First, male rodents engineered to lack (fore-brain) oxytocin receptors no longer discriminate between familiar and unfamiliar females, whereas normal rodents spent more time investigating unfamiliar female rodents versus female rodents with whom they had shared a cage for several days (Macbeth et al, 2009; also see Ferguson et al, 2000Ferguson et al, , 2002. Along similar lines, participants who memorized pictures of faces under oxytocin performed better one day later on measures of familiarity, indicating that oxytocin makes a face in memory more familiar (Rimmele et al, 2009).…”

Importance of the GluN2B carboxy-terminal domain for enhancement of social memories

“…In order to preserve their own colony and strain, mice are more likely to mate within their strain (Macbeth et al 2009). In order to determine the ability of our transgenic mice to form a memory of a mouse of another strain, we tested the animals in a short-term (1 h) and long-term (24 h) social recognition task using white BALB/c juvenile male mice as the stimulus.…”

Impairment of interstrain social recognition during territorial aggressive behavior in oxytocin receptor-null mice

“…In addition to long-term social recognition, rodents are also known to form transient short-term memories of recently encountered individuals (Thor and Holloway, 1982). Since a pioneering study on oxytocinknockout mice by Ferguson and colleagues (Ferguson et al, 2000), it has been revealed that oxytocin receptor (OTR) knockout mice fail to develop short-term memory (Macbeth et al, 2009;Takayanagi et al, 2005) as assessed by a habituation-dishabituation paradigm. In a series of these studies, it was shown that OTR-knockout mice could not distinguish between familiar and novel encounters with mice from the same strain, suggesting that the oxytocin system is involved in "fine" intrastrain recognition in mice (Macbeth et al, 2009).…”

“…Since a pioneering study on oxytocinknockout mice by Ferguson and colleagues (Ferguson et al, 2000), it has been revealed that oxytocin receptor (OTR) knockout mice fail to develop short-term memory (Macbeth et al, 2009;Takayanagi et al, 2005) as assessed by a habituation-dishabituation paradigm. In a series of these studies, it was shown that OTR-knockout mice could not distinguish between familiar and novel encounters with mice from the same strain, suggesting that the oxytocin system is involved in "fine" intrastrain recognition in mice (Macbeth et al, 2009). However, it was shown that OTR-knockout male mice could distinguish between familiar and novel females from different strains in the habituation-dishabituation paradigm, suggesting that the oxytocin system is less important in "broad" interstrain recognition in mice (Macbeth et al, 2009).…”