Altered social interaction in adult rats following neonatal treatment with domoic acid.

Schizophrenia is a debilitating neurological disorder characterized by positive, negative, cognitive and/or emotional symptoms. Decreased social interaction is a common negative symptom. Social interaction can be readily observed in rats and is therefore an ideal target behaviour when evaluating an animal model of schizophrenia. The purpose of this study was to determine whether early alterations in glutamate signaling resulted in social withdrawal; a finding which would be consistent with existing animal models of schizophrenia and is observed within the clinical population. In the present study, male and female SD rat pups received daily injections (s.c.) of very low doses of the glutamate agonist domoic acid (DOM; 20 microg/kg) or saline during a critical period of CNS development (i.e., PND 8-14). As adults, rats were assessed for degree of social interaction. During testing, each test rat was placed in a social interaction arena and scored for social contact with and avoidance of, a same-sex untreated conspecific. No differences were found in overall activity, nor were differences present for time spent engaged in neutral behavior (i.e., not engaged in behaviour, either directed toward or in avoidance of, the stimulus rat). However, domoate-treated male rats demonstrated evidence of social withdrawal, as evidenced by a significantly greater amount of time spent in avoidance behaviour and a significantly less amount of time spent engaged in social contact. These findings are discussed in context of the significance of early alteration to glutamate signaling in the development of human neuropathological disorders.