期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2018.00040
关键词
autoradiography; clozapine; haloperidol; heterodimers; ketamine; proximity ligation assay
资金
- National Science Centre [UMO-14/15/01019]
- Krajowy Naukowy Osrodek Wiodacy (KNOW) funds Ministry of Science and Higher Education [DS-6002-4693-26/WA/12]
G-protein-coupled receptor (GPCR) heterodimers are new targets for the treatment of schizophrenia. Dopamine D-2 receptors and serotonin 5-HT1A and 5-HT2A receptors play an important role in neurotransmission and have been implicated in many human psychiatric disorders, including schizophrenia. Therefore, in this study, we investigated whether antipsychotic drugs (clozapine (CLZ) and haloperidol (HAL)) affected the formation of heterodimers of D-2-5-HT1A receptors as well as 5-HT1A-5-HT2A receptors. Proximity ligation assay (PLA) was used to accurately visualize, for the first time, GPCR heterodimers both at in vitro and ex vivo levels. In line with our previous behavioral studies, we used ketamine to induce cognitive deficits in mice. Our study confirmed the co-localization of D-2/5-HT1A and 5-HT1A/5-HT2A receptors in the mouse cortex. Low-dose CLZ (0.3 mg/kg) administered repeatedly, but not CLZ at 1 mg/kg, increased the level of D-2-5-HT1A and 5-HT1A-5-HT2A heterodimers in the mouse prefrontal and frontal cortex. On the other hand, HAL decreased the level of GPCR heterodimers. Ketamine affected the formation of 5-HT1A-5-HT2A, but not D-2-5-HT1A, heterodimers.
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