Antipsychotic drugs and neuroplasticity: Insights into the treatment and neurobiology of schizophrenia

This paper reviews the evidence that antipsychotic drugs induce neuroplasti city. We outline how the synaptic changes induced by the antipsychotic drug haloperidol may help our understanding of the mechanism of action of antip sychotic drugs in general, and how they may help to elucidate the neurobiol ogy of schizophrenia. Studies have provided compelling evidence that halope ridol induces anatomical and molecular changes in the striatum. Anatomical changes have been documented at the level of regional brain volume, synapse morphology, and synapse number. At the molecular level, haloperidol has be en shown to cause phosphorylation of proteins and to induce gene expression . The molecular responses to conventional antipsychotic drugs are predomina ntly observed in the striatum and nucleus accumbens, whereas atypical antip sychotic drugs have a subtler and more widespread impact. We conclude that the ability of antipsychotic drugs to induce anatomical and molecular chang es in the brain may be relevant for their antipsychotic properties. The del ayed therapeutic action of antipsychotic drugs, together with their promoti on of neuroplasticity suggests that modification of synaptic connections by antipsychotic drugs is important for their mode of action. The concept of schizophrenia as a disorder of synaptic organization will benefit from a be tter understanding of the synaptic changes induced by antipsychotic drugs. (C) 2001 Society of Biological Psychiatry.