Effects of subchronic clozapine treatment on long-term potentiation in rat prefrontal cortex.

Several studies postulated an interaction of clozapine with N-methyl-D-aspartate (NMDA) receptor-mediated transmission. We previously showed that acute clozapine application on rat prefrontal cortex (PFC) slices increased NMDA receptor-dependent long-term potentiation (LTP) in the prelimbic (PL) area. The present study explores the effects of subchronic clozapine treatment on LTP in the same brain area. After 21 days of treatment (30 mg/kg per day, via drinking water), rats were sacrificed and slices from the PFC were prepared for electrophysiological investigations. To this end, extracellular field potentials in the layer II-V pathway were recorded. In contrast to our previous study with acute application on the slice, subchronic clozapine treatment attenuated LTP as compared to non-treated animals. We interpret these findings to suggest that prolonged treatment with clozapine might result in a compensatory response to the acute facilitating action of clozapine on LTP-mediating processes.