International Journal of Molecular Sciences | |
Towards Novel Treatments for Schizophrenia: Molecular and Behavioural Signatures of the Psychotropic Agent SEP-363856 | |
Veronica Begni1  Alice Sanson1  Alessia Luoni1  MarcoA. Riva1  Federica Sensini1  Syeda Munni2  Ben Grayson2  JoannaC. Neill2  | |
[1] Laboratory of Psychopharmacology and Molecular Psychiatry, Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy;Manchester Academic Health Science Centre, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, UK; | |
关键词: schizophrenia; antipsychotic drug; SEP-363856; trace amine-associated receptor; phencyclidine; amphetamine; | |
DOI : 10.3390/ijms22084119 | |
来源: DOAJ |
【 摘 要 】
Schizophrenia is a complex psychopathology whose treatment is still challenging. Given the limitations of existing antipsychotics, there is urgent need for novel drugs with fewer side effects. SEP-363856 (SEP-856) is a novel psychotropic agent currently under phase III clinical investigation for schizophrenia treatment. In this study, we investigated the ability of an acute oral SEP-856 administration to modulate the functional activity of specific brain regions at basal levels and under glutamatergic or dopaminergic-perturbed conditions in adult rats. We found that immediate-early genes (IEGs) expression was strongly upregulated in the prefrontal cortex and, to a less extent, in the ventral hippocampus, suggesting an activation of these regions. Furthermore, SEP-856 was effective in preventing the hyperactivity induced by an acute injection of phencyclidine (PCP), but not of d-amphetamine (AMPH). The compound effectively normalized the PCP-induced increase in IEGs expression in the PFC at all doses tested, whereas only the highest dose determined the major modulations on AMPH-induced changes. Lastly, SEP-856 acute administration corrected the cognitive deficits produced by subchronic PCP administration. Taken together, our data provide further insights on SEP-856, suggesting that modulation of the PFC may represent an important mechanism for the functional and behavioural activity of this novel compound.
【 授权许可】
Unknown