Post-weaning social isolation increases activity in a novel environment but decreases defensive burying and subchronic MK-801 enhances the activity but not the burying effect in rats

Subchronic treatment with a non-competitive glutamate NMDA-receptor antagonist [e.g., MK-801 or phencyclidine] or social isolation (SI) from weaning (age 21 days) to adulthood (age 56 days) produce deficits similar to some of the positive and negative symptoms of schizophrenia. Few studies have evaluated the effects of these treatments on emotional behavior. We hypothesized that subchronic MK-801, post-weaning SI or the two in combination would alter activity in a novel environment, anxiety-like behaviors in the elevated plus-maze, coping responses in the defensive burying paradigm and social behavior. In experiment 1, SI rats (n = 17) showed increased locomotor activity when exposed to a novel environment, no change in plus-maze behavior and decreased defensive burying when compared to group housed rats (n = 16). Subchronic MK-801 enhanced the increase in activity but not the decrease in burying in SI rats. Experiment 2 evaluated the effects on social behavior of post-weaning SI. The locomotor and burying results of experiment 1 were replicated and SI rats (n = 9) were found to decrease orientation towards a novel conspecific social target when compared to group housed rats (n = 8). The behavioral abnormalities of SI rats may be a manifestation of GABAergic dysfunction that has recently become evident in schizophrenia.