Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward
The neurotransmitter acetylcholine has since long been implicated in reward learning and drug addiction. However, the role of specific cholinergic receptor subtypes on different neuronal populations remain elusive. Here, we studied the function of nicotinic acetylcholinergic alpha 7 receptors (α7 nA...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1418686/full |
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| author | Michael Fritz Michael Fritz Michael Fritz Priscila Batista Rosa Daniel Wilhelms Daniel Wilhelms Maarit Jaarola Johan Ruud David Engblom Anna M. Klawonn Anna M. Klawonn Anna M. Klawonn Anna M. Klawonn |
| author_facet | Michael Fritz Michael Fritz Michael Fritz Priscila Batista Rosa Daniel Wilhelms Daniel Wilhelms Maarit Jaarola Johan Ruud David Engblom Anna M. Klawonn Anna M. Klawonn Anna M. Klawonn Anna M. Klawonn |
| author_sort | Michael Fritz |
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| description | The neurotransmitter acetylcholine has since long been implicated in reward learning and drug addiction. However, the role of specific cholinergic receptor subtypes on different neuronal populations remain elusive. Here, we studied the function of nicotinic acetylcholinergic alpha 7 receptors (α7 nAChRs) in cocaine and food-enforced behaviors. We found that global deletion of α7 nAChRs in mice attenuates cocaine seeking in a Pavlovian conditioned place preference paradigm and decreases operant responding to cocaine in a runway task and in self-administration, without influencing responding to palatable food. This effect can be attributed to alpha 7 receptor signaling in the striatum, as selective deletion of striatal α7 nAChRs using a viral vector approach resulted in a similar decrease in cocaine-preference as that of global deletion. To investigate which type of striatal neurons are responsible for this effect, we selectively targeted Cholinergic (ChAT-expressing) neurons and dopamine D1-receptor (D1R) expressing neurons. Mice with conditional deletion of α7 nAChRs in ChAT-neurons (α7 nAChR-ChATCre) exhibited decreased cocaine place preference and intact place preference for food, while α7 nAChR-D1RCre mice had no changes in reward learning to neither food nor cocaine. Cocaine induction of striatal immediate early gene expression of cFos, FosB, Arc and EGR2 was blocked in α7 nAChR-ChATCre mice, demonstrating the importance of α7 nAChRs on cholinergic neurons for striatal neuronal activity changes. Collectively, our findings show that α7 nAChRs on cholinergic interneurons in the striatum are pivotal for learning processes related to cocaine, but not food reward. |
| format | Article |
| id | doaj-art-411108fa4cac4bb9908634614dcf7289 |
| institution | Kabale University |
| issn | 1662-5099 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj-art-411108fa4cac4bb9908634614dcf72892025-01-21T08:36:51ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992025-01-011710.3389/fnmol.2024.14186861418686Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food rewardMichael Fritz0Michael Fritz1Michael Fritz2Priscila Batista Rosa3Daniel Wilhelms4Daniel Wilhelms5Maarit Jaarola6Johan Ruud7David Engblom8Anna M. Klawonn9Anna M. Klawonn10Anna M. Klawonn11Anna M. Klawonn12Department of Biomedical and Clinical Sciences, Linköping University, Linköping, SwedenSchool of Health and Social Sciences, AKAD University of Applied Sciences, Stuttgart, GermanyDepartment for Forensic Psychiatry and Psychotherapy, Ulm University, Ulm, GermanyDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, SwedenDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, SwedenDepartment of Emergency Medicine, Linköping University Hospital, Linköping, SwedenDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, SwedenDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, SwedenDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, SwedenDanish Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United StatesThe neurotransmitter acetylcholine has since long been implicated in reward learning and drug addiction. However, the role of specific cholinergic receptor subtypes on different neuronal populations remain elusive. Here, we studied the function of nicotinic acetylcholinergic alpha 7 receptors (α7 nAChRs) in cocaine and food-enforced behaviors. We found that global deletion of α7 nAChRs in mice attenuates cocaine seeking in a Pavlovian conditioned place preference paradigm and decreases operant responding to cocaine in a runway task and in self-administration, without influencing responding to palatable food. This effect can be attributed to alpha 7 receptor signaling in the striatum, as selective deletion of striatal α7 nAChRs using a viral vector approach resulted in a similar decrease in cocaine-preference as that of global deletion. To investigate which type of striatal neurons are responsible for this effect, we selectively targeted Cholinergic (ChAT-expressing) neurons and dopamine D1-receptor (D1R) expressing neurons. Mice with conditional deletion of α7 nAChRs in ChAT-neurons (α7 nAChR-ChATCre) exhibited decreased cocaine place preference and intact place preference for food, while α7 nAChR-D1RCre mice had no changes in reward learning to neither food nor cocaine. Cocaine induction of striatal immediate early gene expression of cFos, FosB, Arc and EGR2 was blocked in α7 nAChR-ChATCre mice, demonstrating the importance of α7 nAChRs on cholinergic neurons for striatal neuronal activity changes. Collectively, our findings show that α7 nAChRs on cholinergic interneurons in the striatum are pivotal for learning processes related to cocaine, but not food reward.https://www.frontiersin.org/articles/10.3389/fnmol.2024.1418686/fullα7 nicotinic acetylcholine receptorChrna7striatumcocainefood rewardimmediate early genes |
| spellingShingle | Michael Fritz Michael Fritz Michael Fritz Priscila Batista Rosa Daniel Wilhelms Daniel Wilhelms Maarit Jaarola Johan Ruud David Engblom Anna M. Klawonn Anna M. Klawonn Anna M. Klawonn Anna M. Klawonn Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward Frontiers in Molecular Neuroscience α7 nicotinic acetylcholine receptor Chrna7 striatum cocaine food reward immediate early genes |
| title | Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward |
| title_full | Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward |
| title_fullStr | Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward |
| title_full_unstemmed | Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward |
| title_short | Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward |
| title_sort | nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine reinforcement but not food reward |
| topic | α7 nicotinic acetylcholine receptor Chrna7 striatum cocaine food reward immediate early genes |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1418686/full |
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