{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T16:02:05Z","timestamp":1779984125389,"version":"3.53.1"},"update-to":[{"DOI":"10.12688\/f1000research.127830.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000}}],"reference-count":69,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014370","name":"Simons Foundation Autism Research Initiative","doi-asserted-by":"publisher","award":["719401"],"award-info":[{"award-number":["719401"]}],"id":[{"id":"10.13039\/100014370","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03MH103857"],"award-info":[{"award-number":["R03MH103857"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21HD093021"],"award-info":[{"award-number":["R21HD093021"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Altered sensory processing is a pervasive symptom in individuals with Autism Spectrum Disorders (ASD); people with Phelan McDermid syndrome (PMS), in particular, show reduced responses to sensory stimuli. PMS is caused by deletions of the terminal end of chromosome 22 or point mutations in\n                    <ns4:italic>Shank3<\/ns4:italic>\n                    . People with PMS can present with an array of symptoms including ASD, epilepsy, gastrointestinal distress, and reduced responses to sensory stimuli. People with PMS are often medicated to manage behaviors like aggression and\/or self-harm and\/or epilepsy, and it remains unclear how these medications might impact perception\/sensory processing. Here we test this using zebrafish mutant\n                    <ns4:italic>shank3ab<\/ns4:italic>\n                    PMS models that likewise show reduced sensory responses in a visual motor response (VMR) assay, in which increased locomotion is triggered by light to dark transitions.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    We screened three medications, risperidone, lithium chloride (LiCl), and carbamazepine (CBZ), prescribed to people with PMS and one drug, 2-methyl-6-(phenylethynyl) pyridine (MPEP) tested in rodent models of PMS, for their effects on a sensory-induced behavior in two zebrafish PMS models with frameshift mutations in either the N- or C- termini. To test how pharmacological treatments affect the VMR, we exposed larvae to selected drugs for 24 hours and then quantified their locomotion during four ten-minute cycles of lights on-to-off stimuli.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    We found that risperidone partially normalized the VMR in\n                    <ns4:italic>shank3<\/ns4:italic>\n                    models. LiCl and CBZ had no effect on the VMR in any of the three genotypes. MPEP reduced the VMR in wildtype (WT) to levels seen in\n                    <ns4:italic>shank3<\/ns4:italic>\n                    models but caused no changes in either\n                    <ns4:italic>shank3<\/ns4:italic>\n                    model. Finally,\n                    <ns4:italic>shank3<\/ns4:italic>\n                    mutants showed resistance to the seizure-inducing drug pentylenetetrazol (PTZ), at a dosage that results in hyperactive swimming in WT zebrafish.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    Our work shows that the effects of drugs on sensory processing are varied in ways that can be genotype- and drug-dependent.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.127830.2","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T11:35:07Z","timestamp":1695814507000},"page":"84","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Drugs prescribed for Phelan-McDermid syndrome differentially impact sensory behaviors in shank3 zebrafish models."],"prefix":"10.12688","volume":"12","author":[{"given":"Robert A.","family":"Kozol","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5839-807X","authenticated-orcid":false,"given":"Julia E.","family":"Dallman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"759-768","DOI":"10.1016\/j.neuroscience.2004.11.031","article-title":"Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression.","volume":"131","author":"S Baraban","year":"2005","journal-title":"Neuroscience."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s13229-020-00355-0","article-title":"Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism.","volume":"11","author":"M Breen","year":"2020","journal-title":"Mol. 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The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}