Ossato Andrea, Uccelli Licia, Bilel Sabrine, Canazza Isabella, Di Domenico Giovanni, Pasquali Micol, Pupillo Gaia, De Luca Maria Antonietta, Boschi Alessandra, Vincenzi Fabrizio, Rimondo Claudia, Beggiato Sarah, Ferraro Luca, Varani Katia, Borea Pier Andrea, Serpelloni Giovanni, De-Giorgio Fabio, Marti Matteo
Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, Ferrara, Italy.
Section of Legal Medicine, Institute of Public Health, Catholic University of the Sacred Heart, Rome, Italy.
Front Psychiatry. 2017 Aug 4;8:130. doi: 10.3389/fpsyt.2017.00130. eCollection 2017.
JWH-018 and AKB48 are two synthetic cannabinoids (SCBs) belonging to different structural classes and illegally marketed as incense, herbal preparations, or chemical supply for theirs psychoactive cannabis-like effects. Clinical reports from emergency room reported psychomotor agitation as one of the most frequent effects in people assuming SCBs. This study aimed to investigate the psychostimulant properties of JWH-018 and AKB48 in male CD-1 mice and to compare their behavioral and biochemical effects with those caused by cocaine and amphetamine. studies showed that JWH-018 and AKB48, as cocaine and amphetamine, facilitated spontaneous locomotion in mice. These effects were prevented by CB receptor blockade and dopamine (DA) D and D receptors inhibition. SPECT-CT studies on dopamine transporter (DAT) revealed that, as cocaine and amphetamine, JWH-018 and AKB48 decreased the [I]-FP-CIT binding in the mouse striatum. Conversely, competition binding studies revealed that, unlike cocaine and amphetamine, JWH-018 and AKB48 did not bind to mouse or human DAT. Moreover, microdialysis studies showed that the systemic administration of JWH-018, AKB48, cocaine, and amphetamine stimulated DA release in the nucleus accumbens (NAc) shell of freely moving mice. Finally, unlike amphetamine and cocaine, JWH-018 and AKB48 did not induce any changes on spontaneous [H]-DA efflux from murine striatal synaptosomes. The present results suggest that SCBs facilitate striatal DA release possibly with different mechanisms than cocaine and amphetamine. Furthermore, they demonstrate, for the first time, that JWH-018 and AKB48 induce a psychostimulant effect in mice possibly by increasing NAc DA release. These data, according to clinical reports, outline the potential psychostimulant action of SCBs highlighting their possible danger to human health.
JWH - 018和AKB48是两种属于不同结构类别的合成大麻素（SCB），因其类似大麻的精神活性作用而被非法作为熏香、草药制剂或化学用品销售。急诊室的临床报告称，精神运动性激越为服用SCB的人群中最常见的效应之一。本研究旨在探究JWH - 018和AKB48对雄性CD - 1小鼠的精神兴奋特性，并将它们的行为和生化效应与可卡因和苯丙胺所引起的效应进行比较。研究表明，JWH - 018和AKB48与可卡因和苯丙胺一样，能促进小鼠的自发活动。这些效应可通过CB受体阻断以及多巴胺（DA）D1和D2受体抑制来预防。对多巴胺转运体（DAT）的单光子发射计算机断层扫描（SPECT） - CT研究显示，JWH - 018和AKB48与可卡因和苯丙胺一样，会降低小鼠纹状体中[I] - FP - CIT的结合。相反，竞争结合研究表明，与可卡因和苯丙胺不同，JWH - 018和AKB48不与小鼠或人类DAT结合。此外，微透析研究表明，全身给予JWH - 018、AKB48、可卡因和苯丙胺会刺激自由活动小鼠伏隔核（NAc）壳中的DA释放。最后，与苯丙胺和可卡因不同，JWH - 018和AKB48不会引起小鼠纹状体突触体自发[H] - DA外流的任何变化。目前的结果表明，SCB促进纹状体DA释放的机制可能与可卡因和苯丙胺不同。此外，它们首次证明，JWH - 018和AKB48可能通过增加NAc DA释放而在小鼠中诱导精神兴奋效应。根据临床报告，这些数据概述了SCB的潜在精神兴奋作用，突出了它们对人类健康可能存在的危险。
