Effects of the synthetic cannabinoid 5F-AMB on anxiety and recognition memory in mice
N-[[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.
We 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.
Intraperitoneal injection of 5F-AMB (0.3 mg/kg) dramatically decreased locomotor activity in the OF, and this effect was partially reversed by AM251 (3 mg/kg). Intracerebroventricular infusion of 5F-AMB (10 nmol) 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 (1.8 nmol). Bilateral intra-mPFC infusion of 5F-AMB (10 pmol/side) similarly produced impaired recognition memory acquisition, but no anxiolytic effect.
The 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.
Keywords5F-AMB Synthetic cannabinoids Designer drug Medial prefrontal cortex
This study was supported by Grant-in-Aid for Scientific Research (C) (K.K., 15K06765, 18K06520) from the Japan Society for the Promotion of Science (JSPS); Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sport, Science, and Technology of Japan (S.K., 15K15182); grant from Suzuken Memorial Foundation (K.K.); and the Kurata Grant awarded by the Hitachi Global Foundation (K.K.), Hoansha Foundation (K.K.), and Smoking Research Foundation (K.K.).
Compliance with ethical standards
All experiments were performed with the approval of the Institutional Animal Care and Use Committee at Kanazawa University.
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.
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