Selective effects of typical antipsychotic drugs on SNAP-25 and synaptophysin in the hippocampal trisynaptic pathway

Recent studies indicate that levels of presynaptic proteins are altered in the post-mortem brain in schizophrenia. In particular, the hippocampus exhibits reduced levels of synaptophysin and the SNARE protein SNAP-25. The effects of treatment with antipsychotic drugs on levels of SNAP-25 in the hippocampus remains unknown. To determine the effects of typical antipsychotic drugs on levels of synaptophysin and SNAP-25 in the hippocampus, rats were treated with chlorpromazine, haloperidol or trifluoperazine for 21 d. Quantitative immunohistochemistry was used to measure immunoreactivity within the trisynaptic circuit of the hippocampus. Trifluoperazine decreased synaptophysin within the Schaffer collateral region of the radiatum lacunosum in CA1, while haloperidol and chlorpromazine increased SNAP-25 throughout the trisynaptic pathway of the hippocampus, with strongest effects in the mossy fibre region of CA3. These results indicate that presynaptic proteins represent a potential molecular substrate for the effects of antipsychotic drugs on hippocampal synaptic connectivity.