Single cell profiling of the mouse striatum across dorsal-ventral subregions and following chronic clozapine administration

The ventral striatum is posited as a preferential site of antipsychotic action; while acute administration of typical antipsychotics (those associated with extrapyramidal side effects) induces intermediate early gene (IEG) expression in the dorsal striatum, acute administration of atypical antipsychotics preferentially induces IEG expression in the ventral striatum. However, cell type and regional-specific transcriptional changes in striatum in response to antipsychotics remain poorly understood.

We dosed the atypical antipsychotic clozapine on an escalating schedule for six weeks to mimic human administration, and characterized transcriptional effects in the mouse striatum across cell types and subregion (dorsal versus ventral) using single nucleus RNA-sequencing (snRNA-seq).