Effects of the synthetic cannabinoid 5F-AMB on anxiety and recognition memory in mice
Effects of the synthetic cannabinoid 5F-AMB on anxiety and recognition memory in mice
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DOI：
10.1007/s00213-019-05222-2
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发表时间：
2019-07-01
影响因子：
3.4
通讯作者：
Kaneda, Katsuyuki
中科院分区：
文献类型：
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作者：
Ito, Shiho;Deyama, Satoshi;Kaneda, Katsuyuki
N-[[1-（5-氟戊基）-1H-吲唑-3-基]羰基]-1-缬氨酸甲酯（5 F-AMB）是一种合成的大麻素，最近已被分配。虽然吸入5 F-AMB会产生不良反应，如记忆力受损和意识障碍，但在人类中，目的本研究首次观察了5 F-AMB腹腔注射和侧脑室注射对大鼠焦虑样行为、旷场（OF）实验中的自发活动和新物体再认（NOR）实验中的再认记忆的影响。C57 BL/6 J小鼠。我们还研究了大麻素1（CB 1）受体拮抗剂AM 251是否阻断5 F-AMB的作用。接下来，我们研究了5 F-AMB注入到内侧前额叶皮层（mPFC），大脑区域与焦虑和记忆，对这些tests.ResultsIntraperitoneal注射5 F-AMB（0.3mg/kg）显着降低自发活动的OF的影响，这种影响被部分逆转AM 251（3 mg/kg）。侧脑室注射5 F-AMB（10 nmol）可使OF产生抗焦虑作用，并使NOR的再认记忆获得受损，但不影响再认记忆的提取，这些作用可被AM 251（1.8nmol）阻断。5 F-AMB（10 pmol/侧）的双侧内mPFC输注同样产生受损的识别记忆获得，但没有anxiolyticeffect.ConclusionsThe结果表明，中央给药5 F-AMB产生抗焦虑作用和受损的识别记忆获得通过激活CB 1受体，而全身5 F-AMB严重损害运动活动。mPFC参与5 F-AMB诱导的再认记忆获得障碍。然而，其他脑区可能有助于5 F-AMB诱导的抗焦虑作用。
RationaleN-[[1-(5-fluoropentyl)-1H-indazol-3-yl]carbonyl]-l-valine methyl ester (5F-AMB) is a synthetic cannabinoid that has been distributed recently. Although inhalation of 5F-AMB produces adverse effects, such as impaired memory and disturbed consciousness, in humans, the psychopharmacological effects of 5F-AMB in rodents have not been investigated.ObjectivesWe first examined the effects of intraperitoneal and intracerebroventricular injections of 5F-AMB on anxiety-like behavior and locomotor activity in the open field (OF) test and recognition memory in the novel object recognition test (NOR) in C57BL/6J mice. We also examined whether a cannabinoid 1 (CB1) receptor antagonist AM251 blocks the effects of 5F-AMB. We next examined the effects of 5F-AMB infusion into the medial prefrontal cortex (mPFC), a brain region associated with anxiety and memory, on these tests.ResultsIntraperitoneal injection of 5F-AMB (0.3mg/kg) dramatically decreased locomotor activity in the OF, and this effect was partially reversed by AM251 (3mg/kg). Intracerebroventricular infusion of 5F-AMB (10nmol) produced an anxiolytic effect in the OF and impaired acquisition, but not retrieval, of recognition memory in the NOR, and these effects were blocked by co-infusion of AM251 (1.8nmol). Bilateral intra-mPFC infusion of 5F-AMB (10pmol/side) similarly produced impaired recognition memory acquisition, but no anxiolytic effect.ConclusionsThe results demonstrate that centrally administered 5F-AMB produces anxiolytic effect and impaired recognition memory acquisition via activation of CB1 receptors, while systemic 5F-AMB severely impaired locomotor activity. The mPFC is involved in 5F-AMB-induced impairment of recognition memory acquisition. However, other brain region(s) may contribute to the 5F-AMB-induced anxiolytic effect.