{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:52:39Z","timestamp":1790473959593,"version":"4.1.0"},"reference-count":52,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cannabis &amp; Cannabinoid Research"],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objectives:<\/jats:title>\n                    <jats:p>\n                      The cannabinoid receptor 2 (CB2) was previously implicated in brain functions, including complex behaviors. Here, we assessed the role of CB2 in selected swimming behaviors in zebrafish larvae and developed an\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      upscalable whole-organism approach for CB2 ligand screening.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach:<\/jats:title>\n                    <jats:p>\n                      Using CRISPR-Cas9 technology, we generated a novel null allele (\n                      <jats:italic toggle=\"yes\">\n                        cnr2\n                        <jats:sup>upr1<\/jats:sup>\n                      <\/jats:italic>\n                      ) and a stable homozygote-viable loss-of-function (CB2-KO) line. We measured in untreated wild-type and\n                      <jats:italic toggle=\"yes\">\n                        cnr2\n                        <jats:sup>upr1\/upr1<\/jats:sup>\n                      <\/jats:italic>\n                      larvae, photo-dependent (swimming) responses (PDR) and center occupancy (CO) to establish quantifiable anxiety-like parameters. Next, we measured PDR alteration and CO variation while exposing wild-type and mutant animals to an anxiolytic drug (valproic acid [VPA]) or to an anxiogenic drug (pentylenetetrazol [PTZ]). Finally, we treated wild-type and mutant larvae with two CB2-specific agonists (JWH-133 and HU-308) and two CB2-specific antagonists, inverse agonists (AM-630 and SR-144528).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Untreated CB2-KO showed a different PDR than wild-type larvae as well as a decreased CO. VPA treatments diminished swimming activity in all animals but to a lesser extend in mutants. CO was strongly diminished and even more in mutants. PTZ-induced inverted PDR was significantly stronger in light and weaker in dark periods and the CO lower in PTZ-treated mutants. Finally, two of four tested CB2 ligands had a detectable activity in the assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      We showed that larvae lacking CB2 behave differently in complex behaviors that can be assimilated to anxiety-like behaviors. Mutant larvae responded differently to VPA and PTZ treatments, providing\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      evidence of CB2 modulating complex behaviors. We also established an upscalable combined genetic\/behavioral approach in a whole organism that could be further developed for high-throughput drug discovery platforms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/can.2018.0025","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T15:17:29Z","timestamp":1554218249000},"page":"88-101","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Altered Swimming Behaviors in Zebrafish Larvae Lacking Cannabinoid Receptor 2"],"prefix":"10.1177","volume":"4","author":[{"given":"Agnes","family":"Acevedo-Canabal","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, Medical Sciences Campus, University of Puerto Rico (MSC-UPR), San Juan, Puerto Rico."},{"name":"Department of Anatomy and Neurobiology, Institute of Neurobiology, University of Puerto Rico, San Juan, Puerto Rico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Col\u00f3n-Cruz","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Medical Sciences Campus, University of Puerto Rico (MSC-UPR), San Juan, Puerto Rico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Rodriguez-Morales","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Medical Sciences Campus, University of Puerto Rico (MSC-UPR), San Juan, Puerto Rico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav K.","family":"Varshney","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Burgess","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NHGRI\/NIH, Bethesda, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Gonz\u00e1lez-Sep\u00falveda","sequence":"additional","affiliation":[{"name":"Puerto Rico Clinical and Translational Research Consortium, Medical Sciences Campus, University of Puerto Rico (MSC-UPR), San Juan, Puerto Rico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Yudowski","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Medical Sciences Campus, University of Puerto Rico (MSC-UPR), San Juan, Puerto Rico."},{"name":"Department of Anatomy and Neurobiology, Institute of Neurobiology, University of Puerto Rico, San Juan, Puerto Rico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Behra","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Medical Sciences Campus, University of Puerto Rico (MSC-UPR), San Juan, Puerto Rico."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,6,14]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(99)01491-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn4036"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2011.00063"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-017-0029-y"},{"key":"e_1_3_3_6_2","first-page":"29","article-title":"Cannabinoid receptors in the central nervous system: their signaling and roles in disease","volume":"10","author":"Kendall DA","year":"2016","unstructured":"Kendall DA, , Yudowski GA. 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