Effect of antipsychotics on spontaneous hyperactivity and hypersensitivity to MK-801-induced hyperactivity in rats prenatally exposed to methylazoxymethanol.

Exposure to methylazoxymethanol (MAM) at embryonic day 17 (E17) in the rat has been proposed to be a promising model for schizophrenia that mimics behavioural abnormalities and deficits in prefrontal cortex (PFC) networks. In this study, we investigated for the first time the effects of antipsychotics on abnormal behaviours observed in prenatally MAM-exposed rats. We first examined spontaneous and MK-801-induced locomotor activity in an open field in adult E17 MAM- or saline-exposed rats. Then, the effect of single injections of haloperidol, clozapine and risperidone was investigated in MAM- or sham-exposed rats on spontaneous and MK-801 (0.05 mg/kg)-induced hyperactivity. Risperidone more selectively counteracted the spontaneous hyperactivity in MAM than in sham rats, while haloperidol and clozapine induced similar effects on spontaneous locomotion in both groups. The main result of this study is that all the tested antipsychotics were more effective in attenuating the MK-801-induced hyperlocomotion in MAM than in sham rats. These findings further support the validity of E17 MAM exposure as a model for schizophrenia and add to its heuristic value in screening therapies for schizophrenia.