Social memory in mice: Disruption with an NMDA antagonist and attenuation with antipsychotic drugs

Abstract

Social recognition reflects the ability of one animal to learn and remember the identity of another. Animal models of social learning and memory are pertinent to several different CNS diseases involving disruptions in cognition. Moreover, the increased understanding of the basic biology of memory increases the likelihood of discovery of memory-enhancing treatments in these human diseases. In the present study, we investigated the effects of the non-competitive NMDA antagonist ketamine on social recognition in mice across a broad dose range (5–30mg/kg) and time-course (60 min- 7 days). We also tested the ability of two antipsychotic drugs, haloperidol and olanzapine, to block the ketamine effect. Our results show that mice demonstrate social recognition over a several day period, with loss of recognition between 3–7 days. Ketamine disrupts social memory at doses which do not affect task performance. Chronic oral administration of haloperidol or olanzapine attenuates these ketamine-induced effects on social recognition, tending to normalize the memory behavior. The neural mechanisms of these actions are not known, although medial temporal lobe memory systems have been implicated.

d-Serine and a glycine transporter-1 inhibitor enhance social memory in rats

“…Thus, the social recognition test used in the present study might be regarded as a predictor of activity in a certain cognitive domain in patients with schizophrenia. Recently, Gao et al (2009) reported that both olanzapine and haloperidol antagonized ketaminedisrupted social memory in mice. The reason for the discrepancy between the present results and theirs is uncertain.…”

“…Also, the social memory of rodents is reportedly facilitated by several memoryenhancing agents including histamine H3 receptor antagonists, 5-HT6 receptor antagonists, and nicotinic α7 receptor agonists (Fox et al 2005;Van Kampen et al 2004;Loiseau et al 2008). Moreover, NMDA reportedly enhances social recognition, while the blockade of the NMDA receptor using MK-801 or ketamine impairs it Krejcí 2002, 2003;Gao et al 2009), suggesting that NMDA receptor function is involved in the social recognition test and that this test might be suitable for evaluating procognitive effects as well as the improvement of cognitive deficits induced by agents acting on NMDA receptor function. However, the usefulness of the social recognition test as an animal model of schizophrenia has not been pharmacologically validated, and the effects of agents acting on the NMDA receptor have not been tested.…”

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

“…Direct evidence of this was found in a post-natal deletion of GluN1 in which the knockout animals were unable to remember the stimulus partner for even a short amount of time in a habituation-dishabituation paradigm (Belforte et al 2010). Further, Gao et al (2009) found that both short-and long-term social recognition memory were impaired in mice treated with the NMDA antagonist ketamine. Similarly, MK-801 administration also impaired social recognition memory (van der Staay et al 2011).…”

Testing synaptic plasticity in dynamic mate choice decisions: N -methyl d -aspartate receptor blockade disrupts female preference

“…Synaptic plasticity processes within the brain mediate dynamic learning and memory, and a critical component of the glutamatergic signalling underlying this plasticity is NMDAR [11]. Pharmacological disruption of NMDAR results in impaired learning, memory, social cognitive and perceptual processes [11][12][13]; however, NMDAR blockade has never before been used in a mate choice context.…”