{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:07:46Z","timestamp":1774483666308,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>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 (\u03b17 nAChRs) in cocaine and food-enforced behaviors. We found that global deletion of \u03b17 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 \u03b17 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 \u03b17 nAChRs in ChAT-neurons (\u03b17 nAChR-ChATCre) exhibited decreased cocaine place preference and intact place preference for food, while \u03b17 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 \u03b17 nAChR-ChATCre mice, demonstrating the importance of \u03b17 nAChRs on cholinergic neurons for striatal neuronal activity changes. Collectively, our findings show that \u03b17 nAChRs on cholinergic interneurons in the striatum are pivotal for learning processes related to cocaine, but not food reward.<\/jats:p>","DOI":"10.3389\/fnmol.2024.1418686","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T08:38:23Z","timestamp":1737448703000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Nicotinic \u03b17 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward"],"prefix":"10.3389","volume":"17","author":[{"given":"Michael","family":"Fritz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscila Batista","family":"Rosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Wilhelms","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarit","family":"Jaarola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Ruud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Engblom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Klawonn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1152\/physrev.00015.2008","article-title":"Mammalian nicotinic acetylcholine receptors: from structure to function","volume":"89","author":"Albuquerque","year":"2009","journal-title":"Physiol. 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