Project Summary

Patricio O’Donnell, M.D., Ph.D. (Independent Investigator 2003) of Albany Medical College, notes that schizophrenia is a disorder affecting several brain regions, and has been studying how these different regions interact in normal animals, gaining insight on how alterations in some (e.g., the hippocampus) can result in deficits on others (e.g. the dopamine pathways). He now wants to address how interactions among areas involved in schizophrenia are affected in animal models that include a developmental component. A previous model is the neonatal ventral hippocampal lesion, in which behavioral anomalies emerge only after puberty. He has shown that neurons in the prefrontal cortex and nucleus accumbens exhibit an abnormal response to the activation of dopamine projections, which are blocked with subchronic pretreatment with haloperidol. Though the model mimics schizophrenia in the time delay in symptom emergence and the system affected (dopamine) and is reversed by an antipsychotic, it involves a lesion in the hippocampus which schizophrenia patients do not have. Dr. O’Donnell recently modified the model with a transient neonatal inactivation instead of a lesion by injecting a compound that blocks neural activity (tetrodotoxin, TTX; a blocker of ion channels involved in nerve conduction that does not kill neurons). It has been shown to elicit similar behavioral changes to those observed with the lesion. He will now further study this non-lesion model to determine if the results are similar to what was observed with a lesion model. If so, the transient inactivation may prove a useful and more valid model. Such a model could be a useful tool to test new antipsychotic drugs.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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