Low dose MK-801 reduces social investigation in mice

Abstract

To characterize MK-801’s effect on social behavior in mice, we examined adult male ICR mice for interaction with companion mice (juvenile male). Test mice were injected with either saline or MK-801 (0.1 mg/kg), and were tested 30 min later for their social behavior during a 5-min session. A second encounter took place 30 min later, with either a familiar companion mouse (the same as in the initial encounter) or a novel mouse. In saline controls, second encounter with a familiar companion mouse showed reduced social investigative behaviors (anogenital sniffing and staying together), indicating habituation toward a familiar mouse. Second encounter with a novel companion mouse did not show habituation in social investigative behaviors. Pretreatment with MK-801 reduced anogenital sniffing during the first encounter. At the second encounter, these mice displayed non-discriminative habituation of social investigative behaviors, with reduced anogenital sniffing and staying together, regardless of whether the companion mouse was a familiar or a novel one. These results indicate that MK-801 affected exploratory activities of mice, resulting in both reduced social investigative behaviors during first encounter with a companion mouse, and diminished discriminative capacities for a familiar vs. a novel companion mouse during subsequent encounter.

Subchronic pharmacological and chronic genetic NMDA receptor hypofunction differentially regulate the Akt signaling pathway and Arc expression in juvenile and adult mice

“…Furthermore, SR−/− mice have many of the same brain morphological abnormalities observed in schizophrenia, such as reduced cortico-hippocampal volume, decreased dendritic spine density (Balu et al, 2012; Balu et al, 2013) and increased lateral ventricles (Puhl et al, 2015). Pharmacological NMDAR hypofunction models produce hyperlocomotion and stereotypy (Hoffman, 1992), as well as social withdrawal (Zou et al, 2008), behavioral abnormalities that are not observed in SR−/− mice (Basu et al, 2009; DeVito et al, 2011). Thus, the SR−/− mice exhibit a forebrain NMDA receptor hypofunction endophenotype with cortical neuronal atrophy associated with negative symptoms and cognitive but not with several behavioral abnormalities linked to psychosis.…”

“…Therefore, NMDAR antagonists have been used as a tool to induce NMDAR hypofunction in experimental animals as a pharmacologic model of schizophrenia (Adell et al, 2012; Eyjolfsson et al, 2006; Javitt and Zukin, 1991; Wiescholleck and Manahan-Vaughan, 2013). These pharmacological models exhibit hyperlocomotion, stereotypies (Hoffman, 1992) and social withdrawal (Zou et al, 2008), as well as long-term potentiation (LTP) and learning deficits (Manahan-Vaughan et al, 2008). …”

Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia

“…While not as well studied as social interaction, there have been several research studies analyzing impaired social recognition in animal models of schizophrenia. For example, acute treatment with MK-801 (0.1 mg/kg) produced diminished discriminative capabilities for a familiar versus novel conspecific in both male rats and mice (Zou et al, 2008). Additionally, pretreatment with clozapine (0.3–1 mg/kg), but not haloperidol (0.01–0.1 mg/kg), significantly attenuated the effects of MK-801 in male rats (Shimazaki et al, 2010).…”

Autism-like Deficits in Shank3-Deficient Mice Are Rescued by Targeting Actin Regulators

“…Recent evidence has implicated NMDAR dysfunction in ASD (Carlson, 2012). Administration of NMDAR antagonists or NR1 deficiency induces ASD-like social deficits in mice (Zou et al, 2008). Shank2 or Shank3 -lacking mice exhibit impaired NMDAR-dependent synaptic plasticity along with ASD-related behaviors (Wang et al, 2011; Won et al, 2012; Kouser et al, 2013).…”