Schizophrenia-like olfactory dysfunction induced by acute and postnatal phencyclidine exposure in rats.

Deficits in olfactory abilities are frequently observed in schizophrenia patients. However, whether olfactory dysfunction is found in animal models is not known. Here, we examined whether two well-established schizophrenia rat models exhibit olfactory-relevant dysfunction that is similar to schizophrenia patients. Olfactory sensitivity was tested in rats that were acutely (3.3mg/kg) or postnatally (10mg/kg, at postnatal day 7, 9 and 11) treated with phencyclidine (PCP) as schizophrenia models. Electrophysiological recordings were conducted to measure the olfactory-relevant local field potential after acute PCP treatment. Olfactory-relevant neural connections were tested via virus tracing in rats postnatally treated with PCP. We also assessed the reversal effects of olanzapine (OLZ) treatment on both models. We found that acute PCP treatment induced a decline in olfactory sensitivity (p=0.01) and significantly lower beta- and higher gamma-band oscillations (p=0.03, and p=0.00 respectively) which were partly attenuated by OLZ treatment (2mg/kg and 4mg/kg). Postnatal PCP exposure also resulted in an olfactory sensitivity deficit during adulthood (p=0.012 for males and p=0.009 for females), and an abnormal development of neural circuits (p=0.000). Together, our research indicated that olfactory dysfunction found in schizophrenia patients can also be observed on animal models.