cDNA array reveals differential gene expression following chronic neuroleptic administration: implications of synapsin II in haloperidol treatment

The cDNA expression array is a recently developed scientific tool that can profile the differential expression of several hundreds of genes simultaneously and is therefore advantageous in the study of antipsychotic drug action at the genetic level. Using this technology, we discovered 14 genes in the rat striatum whose expression was changed by greater than or equal to 50% following chronic haloperidol treatment. Among them was the synapsin II gene, which was found to be significantly up-regulated after the treatment. Since recent studies have implicated this gene in schizophrenia, further experiments were performed to determine whether chronic haloperidol exposure resulted in concurrent increases in the expression of striatal synapsin II protein. Immunoblotting revealed that protein levels of both the a and b isoforms of synapsin II were also increased by comparable amounts following haloperidol treatment. This study is the first to show the regulation of synapsin II expression by haloperidol at the transcript and protein level in rat striatum. A possible mechanism for the observed haloperidol-induced increase in striatal synapsin II expression, along with the implications of this up-regulation in chronic haloperidol treatment, is presented.