Social dysfunction in the neurodevelopmental model of schizophrenia in male and female rats: Behavioural and biochemical studies

Social dysfunction is among the core symptoms of schizophrenia. The neuropeptides oxytocin (OXT) and vasopressin (VP) are involved in the regulation of social behaviour and social cognition. There are indications that both of these neurotransmitter systems are altered in schizophrenia. Prenatal (embryonic day 17) exposure to the neurotoxin methylazoxymethanol acetate (MAM; 22 mg/kg) leads to a schizophrenia-like phenotype in rats and has been used as a model of schizophrenia symptoms. Here, we examined the social phenotype of MAM-exposed female and male rats and measured concentrations of OXT, VP and their specific receptors in various brain areas involved in the control of social behaviour. We report decreases in social behaviour and ultrasonic vocalisations (USVs) in the MAM rats during social encounters. Specifically, the duration of social interactions and number of corresponding USVs were reduced in this group. In the MAM rats, "positive" 50-kHz USVs were flatter, i.e., displayed lower bandwidth, a greater percentage of "short" calls and lower percentage of frequency-modulated calls. The MAM animals exhibited diminished interest towards social stimuli in olfactory preference tests. In the resident-intruder test, MAM exposure reduced dominance behaviour only in the males. We also report cognitive impairments, including reduced novel object recognition and cognitive inflexibility in the attentional set shifting test, and decreased OXT and OXT receptor concentrations in the prefrontal cortex and hypothalamus and VP and VP receptors in the hypothalamus in the MAM rats. Deficits in central OXT and VP systems may underlie abnormalities present in the MAM model of schizophrenia.