What is it about?

Prepulse inhibition (PPI) of the startle response is a measure of sensorimotor gating that is impaired in many clinical conditions, including schizophrenia. The inbred Roman high-avoidance (RHA) rats, compared to their low-avoidance (RLA) counterparts, show distinct schizophrenia-like phenotypes, such as spontaneous deficits in PPI accompanied by decreased medial prefrontal cortex (mPFC) activity and volume. Schizophrenia-like deficits are usually attenuated by antipsychotic drugs, but these drugs often produce severe side effects. In order to reduce these side effects, the neuropeptide oxytocin has been proposed as an alternative natural antipsychotic for schizophrenia. Here, we examined the effects of peripheral oxytocin administration (saline, 0.04, and 0.2mg/kg) on PPI in the RHA vs. RLA rats, as well as in the outbred heterogeneous stock (HS) rats. Our results showed that oxytocin increased PPI in the HS rats and attenuated PPI deficits in the RHA rats, but it did not significantly affect PPI in the RLAs. To explore whether these divergent effects associated with differences in oxytocinergic mechanisms, we analyzed gene expression of the oxytocin receptor (OXTR) and the regulator of oxytocin release (CD38) in the mPFC of the Roman rats. Consistent with the differential oxytocin effects on PPI (RHA>RLA), constitutive CD38 expression was reduced in the RHA rats compared to the RLAs, while oxytocin administration increased OXTR expression in both strains. Overall, the present work reveals that oxytocin administration shows antipsychotic-like effects on PPI in outbred and inbred rats, and it suggests that these effects may be related to basal differences in oxytocin-mediated mechanisms in the mPFC.

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Why is it important?

This research is important because it highlights oxytocin as a potential safer alternative to traditional antipsychotics for schizophrenia, offering fewer side effects and targeting symptoms like social deficits and sensorimotor gating impairments. It also underscores the role of genetic factors, such as CD38 expression, in predicting treatment efficacy, paving the way for personalized medicine. With schizophrenia being difficult to treat effectively, this study provides a promising new avenue for improving patient outcomes.

Perspectives

Oxytocin offers a promising new perspective in the treatment of schizophrenia, particularly for addressing symptoms like social cognitive deficits and negative symptoms that are often resistant to traditional antipsychotics. Its unique mechanism of action, better safety profile, and fewer side effects make it an attractive alternative or adjunctive therapy. The potential for personalized medicine is significant, as genetic factors like oxytocin receptor (OXTR) and CD38 expression could help predict treatment efficacy. Intranasal oxytocin delivery also provides a convenient, non-invasive method for administration. However, while early findings are encouraging, further research and clinical trials are needed to confirm its long-term safety and efficacy, as well as to optimize its use in combination with existing treatments.

Carles Tapias Espinosa

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This page is a summary of: Oxytocin attenuates schizophrenia-like reduced sensorimotor gating in outbred and inbred rats in line with strain differences in CD38 gene expression, Physiology & Behavior, October 2021, Elsevier,
DOI: 10.1016/j.physbeh.2021.113547.
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