Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex
G-protein–coupled receptor (GPCR) heterodimers are new targets for the treatment of schizophrenia. Dopamine D2 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. Theref...
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| Format: | Article |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00040/full |
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| author | Marta Szlachta Maciej Kuśmider Paulina Pabian Joanna Solich Magdalena Kolasa Dariusz Żurawek Marta Dziedzicka-Wasylewska Agata Faron-Górecka |
| author_facet | Marta Szlachta Maciej Kuśmider Paulina Pabian Joanna Solich Magdalena Kolasa Dariusz Żurawek Marta Dziedzicka-Wasylewska Agata Faron-Górecka |
| author_sort | Marta Szlachta |
| collection | DOAJ |
| description | G-protein–coupled receptor (GPCR) heterodimers are new targets for the treatment of schizophrenia. Dopamine D2 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 D2–5-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 D2/5-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 D2–5-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 D2–5-HT1A, heterodimers. |
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| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-22T08:28:08Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-f47e84f4006f4a30ba9b60518edb39e02022-12-21T18:32:34ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-02-011110.3389/fnmol.2018.00040330494Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse CortexMarta Szlachta0Maciej Kuśmider1Paulina Pabian2Joanna Solich3Magdalena Kolasa4Dariusz Żurawek5Marta Dziedzicka-Wasylewska6Agata Faron-Górecka7epartment of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Polandepartment of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Polandepartment of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Polandepartment of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Polandepartment of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Polandepartment of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Polandepartment of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Polandepartment of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, PolandG-protein–coupled receptor (GPCR) heterodimers are new targets for the treatment of schizophrenia. Dopamine D2 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 D2–5-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 D2/5-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 D2–5-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 D2–5-HT1A, heterodimers.http://journal.frontiersin.org/article/10.3389/fnmol.2018.00040/fullautoradiographyclozapinehaloperidolheterodimersketamineproximity ligation assay |
| spellingShingle | Marta Szlachta Maciej Kuśmider Paulina Pabian Joanna Solich Magdalena Kolasa Dariusz Żurawek Marta Dziedzicka-Wasylewska Agata Faron-Górecka Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex Frontiers in Molecular Neuroscience autoradiography clozapine haloperidol heterodimers ketamine proximity ligation assay |
| title | Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex |
| title_full | Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex |
| title_fullStr | Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex |
| title_full_unstemmed | Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex |
| title_short | Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex |
| title_sort | repeated clozapine increases the level of serotonin 5 ht1ar heterodimerization with 5 ht2a or dopamine d2 receptors in the mouse cortex |
| topic | autoradiography clozapine haloperidol heterodimers ketamine proximity ligation assay |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00040/full |
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