Allopregnanolone infused into the dorsal (CA1) hippocampus increases prepulse inhibition of startle response in Wistar rats

The hippocampus is a brain structure that has traditionally been associated with the pathophysiology and neuropathology of schizophrenia. Also, one of the animal models of schizophrenia most widely accepted and validated is the deterioration of prepulse inhibition (PPI). The hippocampus (both dorsal and ventral) seems to be a brain structure important for the PPI since it appears to contribute to sensorimotor gating. A possible role of neurosteroids in schizophrenia has recently been suggested, as clozapine and olanzapine treatments increase brain and plasma levels of the neurosteroid allopregnanolone (AlloP). The aim of the present work is to investigate the effects of the intrahippocampal administration of neurosteroids on prepulse inhibition. For this purpose, we have bilaterally injected AlloP (0.2μg/0.5μl) and pregnenolone sulphate (PregS, 5ng/0.5μl) into the dorsal CA1 hippocampus, and we have evaluated PPI behavior. Results show that intrahippocampal AlloP increases PPI ability regardless of prepulse intensity (5, 10 or 15. db above background). Intrahippocampal PregS administration, at the dose tested, does not significantly affect PPI performance. The increase in PPI due to intrahippocampal AlloP administration points out the important role of the hippocampus in central sensorimotor gating mechanisms and on the effects of neurosteroids on this behavior. The present findings may contribute to the study of the neurobiological basis of schizophrenia. © 2011 Elsevier Ltd.