A Novel Neighbor Housing Environment Enhances Social Interaction and Rescues Cognitive Deficits from Social Isolation in Adolescence.

Adolescence is characterized by high levels of playful social interaction, cognitive development, and increased risk-taking behavior. Juvenile exposure to social isolation or social stress can reduce myelin content in the frontal cortex, alter neuronal excitability, and disrupt hypothalamic pituitary adrenal (HPA) axis function. As compared to group housed animals, social isolation increases anxiety-like phenotypes and reduces social and cognitive performance in adulthood. We designed a neighbor housing environment to alleviate issues related to social isolation that still allowed individual homecages. Neighbor housing consists of four standard mouse cages fused together with semi-permeable ports that allow visual, olfactory, and limited social contact between mice. Adolescent C57BL/6J males and females were group housed (4/cage), single housed (1/cage), or neighbor housed (4/complex). As adults, mice were tested for social, anxiety-like, and cognitive behaviors. Living in this neighbor environment reduced anxiety-like behavior in the social interaction task and in the light-dark task. It also rescued cognitive deficits from single housing in the novel object recognition task. These data suggest that neighbor housing may partially ameliorate the social anxiety and cognitive deficits induced by social isolation. These neighbor cage environments may serve as a conduit by which researchers can house mice in individual cages while still enabling limited social interactions to better model typical adolescent development.

Role of mGlu2 in the 5-HT2A receptor-dependent antipsychotic activity of clozapine in mice.

BACKGROUND: Serotonin 5-HT2A and metabotropic glutamate 2 (mGlu2) are neurotransmitter G protein-coupled receptors (GPCRs) involved in the signaling mechanisms underlying psychosis and schizophrenia treatment. Previous findings in mGlu2 knockout (KO) mice suggested that mGlu2 is necessary for head-twitch behavior, a rodent phenotype characteristic of hallucinogenic 5-HT2A receptor agonists. However, the role of mGlu2 in the behavioral effects induced by antipsychotic drugs remains poorly understood. Here, we tested antipsychotic-like behavioral phenotypes induced by the atypical antipsychotic clozapine in mGlu2-KO mice and wild-type control littermates. METHODS: Locomotor activity was tested in mGlu2-KO mice and control littermates injected (i.p.) with clozapine (1.5 mg/kg) or vehicle followed by MK801 (0.5 mg/kg), PCP (7.5 mg/kg), amphetamine (6 mg/kg), scopolamine (2 mg/kg), or vehicle. Using a virally (HSV) mediated transgene expression approach, the role of frontal cortex mGlu2 in the modulation of MK801-induced locomotor activity by clozapine treatment was also evaluated. RESULTS: The effect of clozapine on hyperlocomotor activity induced by the dissociative drugs MK801 and phencyclidine (PCP) was decreased in mGlu2-KO mice as compared to controls. Clozapine treatment, however, reduced hyperlocomotor activity induced by the stimulant drug amphetamine and the deliriant drug scopolamine in both wild-type and mGlu2-KO mice. Virally mediated over-expression of mGlu2 in the frontal cortex of mGlu2-KO mice rescued the ability of clozapine to reduce MK801-induced hyperlocomotion. CONCLUSION: These findings further support the existence of a functionally relevant crosstalk between 5-HT2A and mGlu2 receptors in different preclinical models of antipsychotic activity.