Ultrasonic vocalisations explain unexpected effects on pre-pulse inhibition responses in rats chronically pre-treated...

Deficits in pre-pulse inhibition (PPI-indicative of psychosis in humans) can be replicated in rats using the NMDA receptor antagonist phencyclidine (PCP). Ultrasonic vocalisations (USVs) produced by rats in response to acoustic startle are indicative of heightened anxiety; here we tested the predictive validity of USVs as an indicator of PPI. Male juvenile Sprague-Dawley rats (n=10) were treated for 14 days with either PCP (5mg/kg i.p.) or saline controls (1 ml/kg i.p.). PPI responses and USVs were recorded on days 16 and 19. PCP-treated rats showed decreased PPI performance on day 16 compared to controls; an observation that was unexpectedly reversed on day 19. Call parameters indicated that both treatment groups experienced similar levels of anxiety in response to the PPI paradigm on day 16. On day 19, the controls showed increased call duration and latency to onset (LtO) of calling, but decreased in the total number of calls produced compared to day 16. The calling period was significantly reduced compared to PCP-treated animals on say 19, whilst the LtO and duration were significantly increased. These changes were considered indicative of heightened levels of anxiety, most likely due to inadvertent fear conditioning (supported by reduced PPI performance) acquired during PPI testing. In contrast, the stability of USV characteristics emitted by PCP treated animals likely signified the detrimental effects of chronic PCP treatment on working memory. These results suggest that USVs are a valuable additional measure during PPI testing, helping to explain the unexpected results from our control group.