{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T18:23:38Z","timestamp":1778783018201,"version":"3.51.4"},"reference-count":61,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T00:00:00Z","timestamp":1209081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2008,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Antipsychotic drugs produce acute behavioral effects through antagonism of dopamine and serotonin receptors, and long\u2010term adaptive responses that are not well understood. The goal of the study presented here was to use <jats:italic>Caenorhabditis elegans<\/jats:italic> to investigate the molecular mechanism or mechanisms that contribute to adaptive responses produced by antipsychotic drugs. First\u2010generation antipsychotics, trifluoperazine and fluphenazine, and second\u2010generation drugs, clozapine and olanzapine, increased the expression of tryptophan hydroxylase\u20101::green fluorescent protein (TPH\u20101::GFP) and serotonin in the ADF neurons of <jats:italic>C. elegans<\/jats:italic>. This response was absent or diminished in mutant strains lacking the transient receptor potential vanilloid channel (TRPV; <jats:italic>osm\u20109<\/jats:italic>) or calcium\/calmodulin\u2010dependent protein kinase II (CaMKII; <jats:italic>unc\u201043<\/jats:italic>). The role of calcium signaling was further implicated by the finding that a selective antagonist of calmodulin and a calcineurin inhibitor also enhanced TPH\u20101::GFP expression. The ADF neurons modulate foraging behavior (turns\/reversals off food) through serotonin production. We found that short\u2010term exposure to the antipsychotic drugs altered the frequency of turns\/reversals off food. This response was mediated through dopamine and serotonin receptors and was abolished in serotonin\u2010deficient mutants (<jats:italic>tph\u20101<\/jats:italic>) and strains lacking the SER\u20101 and MOD\u20101 serotonin receptors. Consistent with the increase in serotonin in the ADF neurons induced by the drugs, drug withdrawal after 24\u2010hr treatment was accompanied by a rebound in the number of turns\/reversals, which demonstrates behavioral adaptation in serotonergic systems. Characterization of the cellular, molecular, and behavioral adaptations to continuous exposure to antipsychotic drugs may provide insight into the long\u2010term clinical effects of these medications. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21684","type":"journal-article","created":{"date-parts":[[2008,4,26]],"date-time":"2008-04-26T00:17:00Z","timestamp":1209169020000},"page":"2553-2563","source":"Crossref","is-referenced-by-count":26,"title":["Antipsychotic drugs up\u2010regulate tryptophan hydroxylase in ADF neurons of <i>Caenorhabditis elegans<\/i>: Role of calcium\u2010calmodulin\u2010dependent protein kinase II and transient receptor potential vanilloid channel"],"prefix":"10.1002","volume":"86","author":[{"given":"Dallas 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