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<!DOCTYPE html> <html lang="en" class="no-js"> <head> <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width, initial-scale=1"> <meta name="robots" content="max-image-preview:large"> <meta name="access" content="No"> <meta name="360-site-verification" content="1268d79b5e96aecf3ff2a7dac04ad990" /> <title>Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on “tetrad”, sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies | Psychopharmacology </title> <meta name="twitter:site" content="@SpringerLink"/> <meta name="twitter:card" content="summary_large_image"/> <meta name="twitter:image:alt" content="Content cover image"/> <meta name="twitter:title" content="Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on “tetrad”, sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies"/> <meta name="twitter:description" content="Psychopharmacology - AKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are marketed as incense,..."/> <meta name="twitter:image" content="https://static-content.springer.com/image/art%3A10.1007%2Fs00213-016-4402-y/MediaObjects/213_2016_4402_Fig1_HTML.gif"/> <meta name="journal_id" content="213"/> <meta name="dc.title" content="Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on “tetrad”, sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies"/> <meta name="dc.source" content="Psychopharmacology 2016 233:21"/> <meta name="dc.format" content="text/html"/> <meta name="dc.publisher" content="Springer"/> <meta name="dc.date" content="2016-08-15"/> <meta name="dc.type" content="OriginalPaper"/> <meta name="dc.language" content="En"/> <meta name="dc.copyright" content="2016 Springer-Verlag Berlin Heidelberg"/> <meta name="dc.rights" content="2016 Springer-Verlag Berlin Heidelberg"/> <meta name="dc.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="dc.description" content="AKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are marketed as incense, herbal preparations or chemical supply for their psychoactive Cannabis-like effects. The present study was aimed at investigating the in vitro and in vivo pharmacological activity of AKB48 and 5F-AKB48 in male CD-1 mice and comparing their in vivo effects with those caused by the administration of Δ9-THC and JWH-018. In vitro competition binding experiments performed on mouse and human CB1 and CB2 receptors revealed a nanomolar affinity and potency of the AKB48 and 5F-AKB48. In vivo studies showed that AKB48 and 5F-AKB48, induced hypothermia, increased pain threshold to both noxious mechanical and thermal stimuli, caused catalepsy, reduced motor activity, impaired sensorimotor responses (visual, acoustic and tactile), caused seizures, myoclonia, hyperreflexia and promoted aggressiveness in mice. Moreover, microdialysis study in freely moving mice showed that systemic administration of AKB48 and 5F-AKB48 stimulated dopamine release in the nucleus accumbens. Behavioural, neurological and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM 251. For the first time, the present study demonstrates the overall pharmacological effects induced by the administration of AKB48 and 5F-AKB48 in mice and suggests that the fluorination can increase the power and/or effectiveness of SCBs. Furthermore, this study outlines the potential detrimental effects of SCBs on human health."/> <meta name="prism.issn" content="1432-2072"/> <meta name="prism.publicationName" content="Psychopharmacology"/> <meta name="prism.publicationDate" content="2016-08-15"/> <meta name="prism.volume" content="233"/> <meta name="prism.number" content="21"/> <meta name="prism.section" content="OriginalPaper"/> <meta name="prism.startingPage" content="3685"/> <meta name="prism.endingPage" content="3709"/> <meta name="prism.copyright" content="2016 Springer-Verlag Berlin Heidelberg"/> <meta name="prism.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="prism.url" content="https://link.springer.com/article/10.1007/s00213-016-4402-y"/> <meta name="prism.doi" content="doi:10.1007/s00213-016-4402-y"/> <meta name="citation_pdf_url" content="https://link.springer.com/content/pdf/10.1007/s00213-016-4402-y.pdf"/> <meta name="citation_fulltext_html_url" content="https://link.springer.com/article/10.1007/s00213-016-4402-y"/> <meta name="citation_journal_title" content="Psychopharmacology"/> <meta name="citation_journal_abbrev" content="Psychopharmacology"/> <meta name="citation_publisher" content="Springer Berlin Heidelberg"/> <meta name="citation_issn" content="1432-2072"/> <meta name="citation_title" content="Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on “tetrad”, sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies"/> <meta name="citation_volume" content="233"/> <meta name="citation_issue" content="21"/> <meta name="citation_publication_date" content="2016/10"/> <meta name="citation_online_date" content="2016/08/15"/> <meta name="citation_firstpage" content="3685"/> <meta name="citation_lastpage" content="3709"/> <meta name="citation_article_type" content="Original Investigation"/> <meta name="citation_language" content="en"/> <meta name="dc.identifier" content="doi:10.1007/s00213-016-4402-y"/> <meta name="DOI" content="10.1007/s00213-016-4402-y"/> <meta name="size" content="438306"/> <meta name="citation_doi" content="10.1007/s00213-016-4402-y"/> <meta name="citation_springer_api_url" content="http://api.springer.com/xmldata/jats?q=doi:10.1007/s00213-016-4402-y&api_key="/> <meta name="description" content="AKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are m"/> <meta name="dc.creator" content="Canazza, Isabella"/> <meta name="dc.creator" content="Ossato, Andrea"/> <meta name="dc.creator" content="Trapella, Claudio"/> <meta name="dc.creator" content="Fantinati, Anna"/> <meta name="dc.creator" content="De Luca, Maria Antonietta"/> <meta name="dc.creator" content="Margiani, Giulia"/> <meta name="dc.creator" content="Vincenzi, Fabrizio"/> <meta name="dc.creator" content="Rimondo, Claudia"/> <meta name="dc.creator" content="Di Rosa, Fabiana"/> <meta name="dc.creator" content="Gregori, Adolfo"/> <meta name="dc.creator" content="Varani, Katia"/> <meta name="dc.creator" content="Borea, Pier Andrea"/> <meta name="dc.creator" content="Serpelloni, Giovanni"/> <meta name="dc.creator" content="Marti, Matteo"/> <meta name="dc.subject" content="Neurosciences"/> <meta name="dc.subject" content="Pharmacology/Toxicology"/> <meta name="dc.subject" content="Psychiatry"/> <meta name="citation_reference" content="citation_journal_title=Neuropharmacology; 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In vitro and in vivo pharmacological studies - Psychopharmacology"/> <meta property="og:description" content="Rationale AKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are marketed as incense, herbal preparations or chemical supply for their psychoactive Cannabis-like effects. Objectives The present study was aimed at investigating the in vitro and in vivo pharmacological activity of AKB48 and 5F-AKB48 in male CD-1 mice and comparing their in vivo effects with those caused by the administration of Δ9-THC and JWH-018. Results In vitro competition binding experiments performed on mouse and human CB1 and CB2 receptors revealed a nanomolar affinity and potency of the AKB48 and 5F-AKB48. In vivo studies showed that AKB48 and 5F-AKB48, induced hypothermia, increased pain threshold to both noxious mechanical and thermal stimuli, caused catalepsy, reduced motor activity, impaired sensorimotor responses (visual, acoustic and tactile), caused seizures, myoclonia, hyperreflexia and promoted aggressiveness in mice. Moreover, microdialysis study in freely moving mice showed that systemic administration of AKB48 and 5F-AKB48 stimulated dopamine release in the nucleus accumbens. Behavioural, neurological and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM 251. Conclusions For the first time, the present study demonstrates the overall pharmacological effects induced by the administration of AKB48 and 5F-AKB48 in mice and suggests that the fluorination can increase the power and/or effectiveness of SCBs. 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In vivo studies showed that AKB48 and 5F-AKB48, induced hypothermia, increased pain threshold to both noxious mechanical and thermal stimuli, caused catalepsy, reduced motor activity, impaired sensorimotor responses (visual, acoustic and tactile), caused seizures, myoclonia, hyperreflexia and promoted aggressiveness in mice. Moreover, microdialysis study in freely moving mice showed that systemic administration of AKB48 and 5F-AKB48 stimulated dopamine release in the nucleus accumbens. Behavioural, neurological and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM 251. For the first time, the present study demonstrates the overall pharmacological effects induced by the administration of AKB48 and 5F-AKB48 in mice and suggests that the fluorination can increase the power and/or effectiveness of SCBs. 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In vitro and in vivo pharmacological studies</h1> <ul class="c-article-identifiers"> <li class="c-article-identifiers__item" data-test="article-category">Original Investigation</li> <li class="c-article-identifiers__item"> Published: <time datetime="2016-08-15">15 August 2016</time> </li> </ul> <ul class="c-article-identifiers c-article-identifiers--cite-list"> <li class="c-article-identifiers__item"> <span data-test="journal-volume">Volume 233</span>, pages 3685–3709, (<span data-test="article-publication-year">2016</span>) </li> <li class="c-article-identifiers__item c-article-identifiers__item--cite"> <a href="#citeas" data-track="click" data-track-action="cite this article" data-track-category="article body" data-track-label="link">Cite this article</a> </li> </ul> <div class="app-article-masthead__buttons" data-test="download-article-link-wrapper" data-track-context="masthead"> </div> </div> <div class="app-article-masthead__brand"> <a href="/journal/213" class="app-article-masthead__journal-link" data-track="click_journal_home" data-track-action="journal homepage" data-track-context="article page" data-track-label="link"> <picture> <source type="image/webp" media="(min-width: 768px)" width="120" height="159" srcset="https://media.springernature.com/w120/springer-static/cover-hires/journal/213?as=webp, https://media.springernature.com/w316/springer-static/cover-hires/journal/213?as=webp 2x"> <img width="72" height="95" src="https://media.springernature.com/w72/springer-static/cover-hires/journal/213?as=webp" srcset="https://media.springernature.com/w144/springer-static/cover-hires/journal/213?as=webp 2x" alt=""> </picture> <span class="app-article-masthead__journal-title">Psychopharmacology</span> </a> <a href="https://link.springer.com/journal/213/aims-and-scope" class="app-article-masthead__submission-link" data-track="click_aims_and_scope" data-track-action="aims and scope" data-track-context="article page" data-track-label="link"> Aims and scope <svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-arrow-right-medium"></use></svg> </a> <a href="https://www.editorialmanager.com/psph/" class="app-article-masthead__submission-link" data-track="click_submit_manuscript" data-track-context="article masthead on springerlink article page" data-track-action="submit manuscript" data-track-label="link"> Submit manuscript <svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-arrow-right-medium"></use></svg> </a> </div> </div> </div> </section> <div class="c-article-main u-container u-mt-24 u-mb-32 l-with-sidebar" id="main-content" data-component="article-container"> <main class="u-serif js-main-column" data-track-component="article body"> <div class="c-article-header"> <header> <ul class="c-article-author-list 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class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Rationale</h3><p>AKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are marketed as incense, herbal preparations or chemical supply for their psychoactive Cannabis-like effects.</p><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Objectives</h3><p>The present study was aimed at investigating the in vitro and in vivo pharmacological activity of AKB48 and 5F-AKB48 in male CD-1 mice and comparing their in vivo effects with those caused by the administration of Δ<sup>9</sup>-THC and JWH-018.</p><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Results</h3><p>In vitro competition binding experiments performed on mouse and human CB<sub>1</sub> and CB<sub>2</sub> receptors revealed a nanomolar affinity and potency of the AKB48 and 5F-AKB48. In vivo studies showed that AKB48 and 5F-AKB48, induced hypothermia, increased pain threshold to both noxious mechanical and thermal stimuli, caused catalepsy, reduced motor activity, impaired sensorimotor responses (visual, acoustic and tactile), caused seizures, myoclonia, hyperreflexia and promoted aggressiveness in mice. Moreover, microdialysis study in freely moving mice showed that systemic administration of AKB48 and 5F-AKB48 stimulated dopamine release in the nucleus accumbens. Behavioural, neurological and neurochemical effects were fully prevented by the selective CB<sub>1</sub> receptor antagonist/inverse agonist AM 251.</p><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Conclusions</h3><p>For the first time, the present study demonstrates the overall pharmacological effects induced by the administration of AKB48 and 5F-AKB48 in mice and suggests that the fluorination can increase the power and/or effectiveness of SCBs. 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class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00213-016-4402-y/MediaObjects/213_2016_4402_Fig12_HTML.gif?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00213-016-4402-y/MediaObjects/213_2016_4402_Fig12_HTML.gif" alt="" loading="lazy"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-13"><figure><figcaption><b id="Fig13" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 13</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00213-016-4402-y/MediaObjects/213_2016_4402_Fig13_HTML.gif?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00213-016-4402-y/MediaObjects/213_2016_4402_Fig13_HTML.gif" alt="" loading="lazy"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-14"><figure><figcaption><b id="Fig14" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 14</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00213-016-4402-y/MediaObjects/213_2016_4402_Fig14_HTML.gif?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00213-016-4402-y/MediaObjects/213_2016_4402_Fig14_HTML.gif" alt="" loading="lazy"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-15"><figure><figcaption><b id="Fig15" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 15</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00213-016-4402-y/MediaObjects/213_2016_4402_Fig15_HTML.gif?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00213-016-4402-y/MediaObjects/213_2016_4402_Fig15_HTML.gif" alt="" loading="lazy"></picture></div></div></figure></div><div class="c-article-section__figure 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data-track-action="click recommendations inline - 3" data-track-label="10.1007/s00213-016-4237-6">Δ<sup>9</sup>-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids in mice and rats </a> </h3> <div class="c-article-meta-recommendations" data-test="recommendation-info"> <span class="c-article-meta-recommendations__item-type">Article</span> <span class="c-article-meta-recommendations__date">15 February 2016</span> </div> </div> </article> </div> </div> </section> <script> window.dataLayer = window.dataLayer || []; window.dataLayer.push({ recommendations: { recommender: 'semantic', model: 'specter', policy_id: 'NA', timestamp: 1740498445, embedded_user: 'null' } }); </script> <section data-title="Abbreviations"><div class="c-article-section" id="abbreviations-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="abbreviations">Abbreviations</h2><div class="c-article-section__content" id="abbreviations-content"><dl class="c-abbreviation_list"><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>AM 251:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>1-(2,4-Dichlorophenyl)-5-(4-iodophenyl)-4-methyl-<i>N</i>-(piperidin-1-yl)-1<i>H</i>-pyrazole-3-carboxamide</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>AKB48:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p> <i>N</i>-(1-Adamantyl)-1-pentyl-1<i>H</i>-indazole-3-carboxamide</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>DA:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Dopamine</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>NAc shell:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Nucleus accumbens shell</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>Δ<sup>9</sup>-THC:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>(−)-Δ<sup>9</sup>-THC or Dronabinol®</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>JWH-018:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Naphthalen-1-yl-(1-pentylindol-3-yl)methanone</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>5F-AKB48:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p> <i>N</i>-(1-Adamantyl)-1-(5-fluoropentyl)-1<i>H</i>-indazole-3- carboxamide</p> </dd></dl></div></div></section><div id="MagazineFulltextArticleBodySuffix"><section aria-labelledby="Bib1" data-title="References"><div class="c-article-section" id="Bib1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" 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Marti) and by local funds from the University of Ferrara to M. Marti. All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in the studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.</p></div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, via Fossato di Mortara 17-19, 44121, Ferrara, Italy</p><p class="c-article-author-affiliation__authors-list">Isabella Canazza, Andrea Ossato & Matteo Marti</p></li><li id="Aff2"><p class="c-article-author-affiliation__address">Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy</p><p class="c-article-author-affiliation__authors-list">Claudio Trapella & Anna Fantinati</p></li><li id="Aff3"><p class="c-article-author-affiliation__address">Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy</p><p class="c-article-author-affiliation__authors-list">Maria Antonietta De Luca & Giulia Margiani</p></li><li id="Aff4"><p class="c-article-author-affiliation__address">Department of Medical Sciences, University of Ferrara, Ferrara, Italy</p><p class="c-article-author-affiliation__authors-list">Fabrizio Vincenzi, Katia Varani & Pier Andrea Borea</p></li><li id="Aff5"><p class="c-article-author-affiliation__address">Department of Diagnostic and Public Health, University of Verona, Verona, Italy</p><p class="c-article-author-affiliation__authors-list">Claudia Rimondo</p></li><li id="Aff6"><p class="c-article-author-affiliation__address">Department of Scientific Investigation (RIS), Carabinieri, 00191, Rome, Italy</p><p class="c-article-author-affiliation__authors-list">Fabiana Di Rosa & Adolfo Gregori</p></li><li id="Aff7"><p class="c-article-author-affiliation__address">U.R.I.To.N., Forensic Toxicology Unit, Department of Health Science, University of Florence, Florence, Italy</p><p class="c-article-author-affiliation__authors-list">Giovanni Serpelloni</p></li><li id="Aff8"><p class="c-article-author-affiliation__address">Center for Neuroscience and Istituto Nazionale di Neuroscienze, ᅟ, Italy</p><p class="c-article-author-affiliation__authors-list">Matteo Marti</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Isabella-Canazza-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Isabella Canazza</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?dc.creator=Isabella%20Canazza" class="c-article-button" data-track="click" data-track-action="author link - 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id="citeas">Cite this article</h3><p class="c-bibliographic-information__citation">Canazza, I., Ossato, A., Trapella, C. <i>et al.</i> Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on “tetrad”, sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies. <i>Psychopharmacology</i> <b>233</b>, 3685–3709 (2016). https://doi.org/10.1007/s00213-016-4402-y</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1007/s00213-016-4402-y?format=refman&flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" data-test="publication-history"><li class="c-bibliographic-information__list-item"><p>Received<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2016-04-26">26 April 2016</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Accepted<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2016-08-01">01 August 2016</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Published<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2016-08-15">15 August 2016</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Issue Date<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2016-10">October 2016</time></span></p></li><li class="c-bibliographic-information__list-item c-bibliographic-information__list-item--full-width"><p><abbr title="Digital Object Identifier">DOI</abbr><span class="u-hide">: </span><span class="c-bibliographic-information__value">https://doi.org/10.1007/s00213-016-4402-y</span></p></li></ul><div data-component="share-box"><div class="c-article-share-box u-display-none" 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class="c-article-subject-list__subject"><span><a href="/search?query=Behavior&facet-discipline="Biomedicine"" data-track="click" data-track-action="view keyword" data-track-label="link">Behavior</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Microdialysis&facet-discipline="Biomedicine"" data-track="click" data-track-action="view keyword" data-track-label="link">Microdialysis</a></span></li></ul><div data-component="article-info-list"></div></div></div></div></div></section> </div> </main> <div class="c-article-sidebar u-text-sm u-hide-print l-with-sidebar__sidebar" id="sidebar" data-container-type="reading-companion" data-track-component="reading companion"> <aside> <div data-test="collections"> </div> <div data-test="editorial-summary"> </div> <div class="c-reading-companion"> <div class="c-reading-companion__sticky" data-component="reading-companion-sticky" data-test="reading-companion-sticky"> <div data-test="access-article" 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