Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments
Brain and Muscle Arnt-like Protein 1 (BMAL1) is an essential component of the molecular clock underlying circadian rhythmicity. Its function has been recently associated with mood and reward processing alterations. We investigated the behavioural and neurobiological impact of Bmal1 gene deletion in...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-09-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222007223 |
| _version_ | 1811338211958456320 |
|---|---|
| author | Adriana Castro-Zavala Laia Alegre-Zurano Lídia Cantacorps Ines Gallego-Landin Patrick-S. Welz Salvador A. Benitah Olga Valverde |
| author_facet | Adriana Castro-Zavala Laia Alegre-Zurano Lídia Cantacorps Ines Gallego-Landin Patrick-S. Welz Salvador A. Benitah Olga Valverde |
| author_sort | Adriana Castro-Zavala |
| collection | DOAJ |
| description | Brain and Muscle Arnt-like Protein 1 (BMAL1) is an essential component of the molecular clock underlying circadian rhythmicity. Its function has been recently associated with mood and reward processing alterations. We investigated the behavioural and neurobiological impact of Bmal1 gene deletion in mice, and how this could affect rewarding effects of cocaine. Additionally, key clock genes and components of the dopamine system were assessed in several brain areas. Our results evidence behavioural alterations in Bmal1-KO mice, including changes in locomotor activity with impaired habituation to environments, short-term memory and social recognition impairments. In addition, Bmal1-KO mice experienced reduced cocaine-induced sensitisation and rewarding effects of cocaine as well as reduced cocaine-seeking behaviour. Furthermore, Bmal1 deletion influenced the expression of other clock-related genes in the mPFC and striatum, as well as alterations in the expression of dopaminergic elements. Overall, the present article offers a novel and extensive characterisation of Bmal1-KO animals. We suggest that reduced cocaine's rewarding effects in these mutant mice might be related to Bmal1 role as an expression regulator of MAO and TH, two essential enzymes involved in dopamine metabolism. |
| first_indexed | 2024-04-13T18:06:43Z |
| format | Article |
| id | doaj.art-9116b799330b4d7d8593fd553c53bf65 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-13T18:06:43Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-9116b799330b4d7d8593fd553c53bf652022-12-22T02:36:03ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-09-01153113333Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairmentsAdriana Castro-Zavala0Laia Alegre-Zurano1Lídia Cantacorps2Ines Gallego-Landin3Patrick-S. Welz4Salvador A. Benitah5Olga Valverde6Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, SpainNeurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, SpainNeurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, SpainNeurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, SpainInstitute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain; Program in Cancer Research, Hospital del Mar Medical Research Institute (IMIM), Barcelona, SpainInstitute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, SpainNeurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, Spain; Neuroscience Research Program, IMIM-Hospital del Mar Research Institute, Barcelona, Spain; Correspondence to: Neurobiology of Behaviour Research Group (GReNeC - NeuroBio), Department of Medicine and Health Sciences, Universitat Pompeu Fabra, Dr. Aiguader 88, Barcelona 08003, Spain.Brain and Muscle Arnt-like Protein 1 (BMAL1) is an essential component of the molecular clock underlying circadian rhythmicity. Its function has been recently associated with mood and reward processing alterations. We investigated the behavioural and neurobiological impact of Bmal1 gene deletion in mice, and how this could affect rewarding effects of cocaine. Additionally, key clock genes and components of the dopamine system were assessed in several brain areas. Our results evidence behavioural alterations in Bmal1-KO mice, including changes in locomotor activity with impaired habituation to environments, short-term memory and social recognition impairments. In addition, Bmal1-KO mice experienced reduced cocaine-induced sensitisation and rewarding effects of cocaine as well as reduced cocaine-seeking behaviour. Furthermore, Bmal1 deletion influenced the expression of other clock-related genes in the mPFC and striatum, as well as alterations in the expression of dopaminergic elements. Overall, the present article offers a novel and extensive characterisation of Bmal1-KO animals. We suggest that reduced cocaine's rewarding effects in these mutant mice might be related to Bmal1 role as an expression regulator of MAO and TH, two essential enzymes involved in dopamine metabolism.http://www.sciencedirect.com/science/article/pii/S0753332222007223Circadian rhythmsBmal1CocaineGluA1GluA2 |
| spellingShingle | Adriana Castro-Zavala Laia Alegre-Zurano Lídia Cantacorps Ines Gallego-Landin Patrick-S. Welz Salvador A. Benitah Olga Valverde Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments Biomedicine & Pharmacotherapy Circadian rhythms Bmal1 Cocaine GluA1 GluA2 |
| title | Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments |
| title_full | Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments |
| title_fullStr | Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments |
| title_full_unstemmed | Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments |
| title_short | Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments |
| title_sort | bmal1 knockout mice exhibit reduced cocaine seeking behaviour and cognitive impairments |
| topic | Circadian rhythms Bmal1 Cocaine GluA1 GluA2 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222007223 |
| work_keys_str_mv | AT adrianacastrozavala bmal1knockoutmiceexhibitreducedcocaineseekingbehaviourandcognitiveimpairments AT laiaalegrezurano bmal1knockoutmiceexhibitreducedcocaineseekingbehaviourandcognitiveimpairments AT lidiacantacorps bmal1knockoutmiceexhibitreducedcocaineseekingbehaviourandcognitiveimpairments AT inesgallegolandin bmal1knockoutmiceexhibitreducedcocaineseekingbehaviourandcognitiveimpairments AT patrickswelz bmal1knockoutmiceexhibitreducedcocaineseekingbehaviourandcognitiveimpairments AT salvadorabenitah bmal1knockoutmiceexhibitreducedcocaineseekingbehaviourandcognitiveimpairments AT olgavalverde bmal1knockoutmiceexhibitreducedcocaineseekingbehaviourandcognitiveimpairments |