{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T03:29:10Z","timestamp":1787974150568,"version":"build-2784847793"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","award":["NS112390"],"award-info":[{"award-number":["NS112390"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:p>The <jats:italic>synaptojanin-1<\/jats:italic> (<jats:italic>SYNJ1<\/jats:italic>) gene is known to be important for dopamine-related disorders. Recent evidence has demonstrated that Synj1 deficient mice (<jats:italic>Synj1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>) have impairments in dopaminergic synaptic vesicular recycling. However, less is known about how <jats:italic>Synj1<\/jats:italic> deficits affect the mesolimbic system, reward processing, and motivated behavior. To examine the role of the <jats:italic>Synj1<\/jats:italic> gene in motivated behavior, we subjected male and female <jats:italic>Synj1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> and <jats:italic>Synj1<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice to a battery of behavioral tests evaluating hedonic responses, effortful responding, and responses to psychomotor stimulants. We observed that <jats:italic>Synj1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice exhibit few differences in reward processing and motivated behavior, with normal hedonic responses and motivated responding for sucrose. However, male but not female <jats:italic>Synj1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> demonstrated an attenuated conditioned place preference for cocaine that could not be attributed to deficits in spatial memory. To further understand the dopamine signaling underlying the attenuated response to cocaine in these mutant mice, we recorded nucleus accumbens dopamine in response to cocaine and observed that <jats:italic>Synj1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> male and female mice took longer to reach peak dopamine release following experimenter-administered cocaine. However, female mice also showed slower decay in accumbens dopamine that appear to be linked to differences in cocaine-induced DAT responses. These findings demonstrate that <jats:italic>SYNJ1<\/jats:italic> deficiencies result in abnormal mesolimbic DA signaling which has not previously been demonstrated. Our work also highlights the need to develop targeted therapeutics capable of restoring deficits in DAT function, which may be effective for reversing the pathologies associated with <jats:italic>Synj1<\/jats:italic> mutations.<\/jats:p>","DOI":"10.3389\/fnbeh.2024.1359225","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T05:10:26Z","timestamp":1720588226000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Haploinsufficiency of the Parkinson\u2019s disease gene synaptojanin1 is associated with abnormal responses to psychomotor stimulants and mesolimbic dopamine signaling"],"prefix":"10.3389","volume":"18","author":[{"given":"Jennifer I.","family":"Mejaes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Saenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina M.","family":"Pizzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Yue","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.biopsych.2006.12.021","article-title":"Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia","volume":"62","author":"Arion","year":"2007","journal-title":"Biol. 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