Current
pharmacotherapy of
schizophrenia remains unsatisfactory with little hope for complete functional restoration in patients once the disease has developed. A preventive approach based on intervention in the
prodromal stage of the disease aiming to preserve functional integrity by halting the progress of the disease is therefore extremely attractive. Here, we investigated the effects of preventive
antipsychotic or
antidepressant drug treatment in a well-established neurodevelopmental mouse model of multiple
schizophrenia-related abnormalities. Pregnant mice on gestation day 9 were exposed to the viral mimic
polyriboinosinic-polyribocytidylic acid (2 mg/kg, intravenously) or corresponding vehicle treatment, and the resulting offspring from both prenatal treatment conditions were subjected to chronic
antipsychotic (
haloperidol or
clozapine),
antidepressant (
fluoxetine), or placebo treatment during the periadolescent stage of development. The effects of the preventive
pharmacotherapy on behavioral and pharmacological functions were then investigated in adulthood using paradigms relevant to
schizophrenia, namely prepulse inhibition, latent inhibition, and sensitivity to psychostimulant drugs. We show that periadolescent treatment with the reference
antipsychotic and
antidepressant drugs can successfully block the emergence of multiple
psychosis-related behavioral and pharmacological abnormalities in subjects predisposed to adult brain pathology by exposure to prenatal immune challenge. At the same time, however, our study reveals numerous negative influences of the early pharmacological intervention on normal behavioral development in control subjects. Hence, even though preventive
pharmacotherapy may be beneficial in individuals with predisposition to
psychosis-related brain dysfunctions, chronic
antipsychotic or
antidepressant drug treatment in false-positive subjects is associated with substantial risk for long-term behavioral disturbances in adulthood.