Journal
PSYCHOPHARMACOLOGY
Volume 236, Issue 7, Pages 2235-2242Publisher
SPRINGER
DOI: 10.1007/s00213-019-05222-2
Keywords
5F-AMB; Synthetic cannabinoids; Designer drug; Medial prefrontal cortex
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Funding
- Japan Society for the Promotion of Science (JSPS) [15K06765, 18K06520]
- Ministry of Education, Culture, Sport, Science, and Technology of Japan [15K15182]
- Suzuken Memorial Foundation
- Hitachi Global Foundation
- Hoansha Foundation
- Smoking Research Foundation
- Grants-in-Aid for Scientific Research [15K06765, 15K15182, 18K06520] Funding Source: KAKEN
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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.
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