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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1418686
This article is part of the Research Topic Mechanisms of Cholinergic Transmission in Motivation and Cognition View all 5 articles

Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward

Provisionally accepted
Michael Fritz Michael Fritz 1Daniel Bjork Wilhelms Daniel Bjork Wilhelms 2Maarit Jaarola Maarit Jaarola 2Johan Ruud Johan Ruud 3David Engblom David Engblom 2Anna Mathia Klawonn Anna Mathia Klawonn 4,5*
  • 1 University of Ulm, Ulm, Baden-Wurttemberg, Germany
  • 2 Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Östergötland, Sweden
  • 3 Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Västergötland, Sweden
  • 4 Danish Research Institute of Translational Neuroscience (DANDRITE), Aarhus, Denmark
  • 5 Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Capital Region of Denmark, Denmark

The final, formatted version of the article will be published soon.

    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.

    Keywords: α7 nicotinic acetylcholine receptor, CHRNA7, Striatum, Cocaine, food reward, Immediate early genes

    Received: 16 Apr 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Fritz, Wilhelms, Jaarola, Ruud, Engblom and Klawonn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Anna Mathia Klawonn, Danish Research Institute of Translational Neuroscience (DANDRITE), Aarhus, Denmark

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