Introduction: Abuse of toluene-containing products by adolescents is a significant public health issue. Our previous study revealed that adolescent toluene exposure produces enduring social deficits and cognitive impairment at adulthood in mice. Antipsychotics are generally used to treat psychotic symptoms in toluene abusers clinically. Objective: The present study examined the predictive validity of this model by evaluating the beneficial effects of antipsychotics on cognitive impairment and social dysfunction after toluene exposure. Materials and methods: Male NMRI mice received injection per day of either toluene (750 mg/kg) or oil at postnatal day P35–P39 and P42–P46. Novel object recognition test and social interaction were conducted after 7-day washout period to confirm the toluene-treated animals with long-lasting behavioral impairment. Thereafter, the acute and subchronic effects of antipsychotics, including haloperidol, clozapine and risperidone were evaluated. Results: All these antipsychotics reduced the social withdrawal, whereas clozapine and risperidone, but not haloperidol, attenuated the cognitive impairment when they were administered 1 h prior to the behavioral tests. Subchronic treatment of antipsychotics for 14 days produced the same improving effects as acute study and the effects lasted at least 14 weeks. These findings suggest that clozapine and risperidone might be better than haloperidol to treat the behavioral disorders related to toluene abuse.
