Poster Presentation The International Congress of Neuroendocrinology 2014

Disruptions in the Oxt system contribute to altered sensorimotor gating (#259)

Megan Rich , Heather Caldwell

One endophenotype of schizophrenia is a lack of sensorimotor gating. Across cross species, sensorimotor gating can be measured using prepulse inhibition (PPI) of the acoustic startle reflex. PPI is regulated by the cortico-striato-pallido-pontine (CSPP) circuit, thus, damage to this circuit results in impaired PPI. We have previously reported that compared to controls, oxytocin knockout (Oxt −/−) mice have larger deficits in PPI following administration of the NMDA receptor antagonist, phencyclidine (PCP). This suggests that endogenous oxytocin (Oxt) may protect against the PPI-disrupting effects of PCP.  These effects do not appear to be regulated by the Oxt receptor (Oxtr), as Oxtr knockout (Oxtr −/−) mice treated with PCP look similar to controls. To confirm that PCP-induced PPI deficits in Oxt −/− mice are due to the absence of Oxt, we attempted to rescue PPI in Oxt −/− mice by intracerebroventricularly administering Oxt prior to treatment with PCP. We also quantified NMDA expression within the CSPP circuit in Oxt −/− mice, Oxtr −/− mice, and controls, since glutamate signaling is important to the functioning of the CSPP circuitry. We found that pretreatment with Oxt was able to partially rescue PCP-induced disruptions of PPI in Oxt −/− mice. We also found that NMDAR1 are downregulated in the amygdala of Oxt −/− mice, but not in Oxtr −/− mice. Our preliminary data also suggest that there are no differences in the expression of NMDR2A and NMDR2B between the aforementioned groups. Taken together, these data continue to support the hypothesis that disruptions in Oxt signaling, and Oxt interactions with the glutamate system, may contribute to altered sensorimotor gating. Since there is evidence of Oxt dysregulation in schizophrenic patients, which may contribute to altered sensorimotor gating, our findings provide a mechanism through which the Oxt system may interact with the CSPP circuitry.