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Social amnesia in mice lacking the oxytocin gene


The development of social familiarity in rodents depends predominantly on olfactory cues and can critically influence reproductive success1,2. Researchers have operationally defined this memory by a reliable decrease in olfactory investigation in repeated or prolonged encounters with a conspecific3,4,5,6. Brain oxytocin (OT) and vasopressin (AVP) seem to modulate a range of social behaviour from parental care to mate guarding7. Pharmacological studies indicate that AVP administration may enhance social memory8,9,10, whereas OT administration may either inhibit or facilitate social memory depending on dose, route or paradigm1,11,12,13. We found that male mice mutant for the oxytocin gene (Oxt−/−) failed to develop social memory, whereas wild-type (Oxt+/+) mice showed intact social memory. Measurement of both olfactory foraging and olfactory habituation tasks indicated that olfactory detection of non-social stimuli is intact in Oxt−/− mice. Spatial memory and behavioural inhibition measured in a Morris water-maze, Y-maze, or habituation of an acoustic startle also seemed intact. Treatment with OT but not AVP rescued social memory in Oxt−/− mice, and treatment with an OT antagonist produced a social amnesia-like effect in Oxt+/+ mice. Our data indicate that OT is necessary for the normal development of social memory in mice and support the hypothesis that social memory has a neural basis distinct from other forms of memory.

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Portions of this research were supported by National Institute of Health Yerkes Regional Primate Research Center Base Grant RR0016, National Institute of Mental Health Grant RO1-M-56538-01 and funds from the National Alliance for Autism Research. The Oxt−/− mice were initially generated with funds from National Institute of Health grant HD33438.

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Correspondence to James T. Winslow.

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Figure 1: Social memory in mice.
Figure 2: Olfaction and habituation tests.
Figure 3: Performance in spatial memory tests.
Figure 4: Pharmacological studies.