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| Página principal > Artículos > Artículos publicados > Oxytocin attenuates schizophrenia-like reduced sensorimotor gating in outbred and inbred rats in line with strain differences in CD38 gene expression |
(Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Research Laboratory for Stereology and Neuroscience, Bispebjerg Copenhagen University Hospital) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)| Fecha: | 2021 |
| Resumen: | 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. 2 mg/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 were 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. |
| Ayudas: | Agencia Estatal de Investigación PSI2017-82257-P Agencia Estatal de Investigación PID2020-114697GB-I00 Ministerio de Educación, Cultura y Deporte FPU15/06307 Agencia Estatal de Investigación FJC2018-038808-I Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR-1586 |
| Derechos: | Tots els drets reservats.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió acceptada per publicar |
| Materia: | CD38 ; OXTR ; Oxytocin ; Schizophrenia ; Sensorimotor gating |
| Publicado en: | Physiology & Behavior, Vol. 240 (Oct. 2021) , art. 113547, ISSN 0031-9384 |
