title: A new designer drug 5F-ADB activates midbrain dopaminergic neurons but not serotonergic neurons.
abstract: N-[[1-(5-fluoropentyl)-1H-indazol-3-yl]carbonyl]-3-methyl-D-valine methyl ester (5F-ADB) is one of the most potent synthetic cannabinoids and elicits severe psychotic symptoms in humans, sometimes causing death. To investigate the neuronal mechanisms underlying its toxicity, we examined the effects of 5F-ADB on midbrain dopaminergic and serotonergic systems, which modulate various basic brain functions such as those in reward-related behavior. 5F-ADB-induced changes in spontaneous firing activity of dopaminergic and serotonergic neurons were recorded by ex vivo electrophysiological techniques. In dopaminergic neurons, 5F-ADB (1 μM) significantly increased the spontaneous firing rate, while 5F-ADB failed to activate dopaminergic neurons in the presence of the CB1antagonist AM251 (1 μM). However, the same concentration of 5F-ADB did not affect serotonergic-neuron activity. These results suggest that 5F-ADB activates local CB1receptors and potentiates midbrain dopaminergic systems with no direct effects on midbrain serotonergic systems.
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Asaoka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawai
authors.forename: Naoya
authors.initials: N
authors.lastname: Nishitani
authors.forename: Haruko
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Norihiro
authors.initials: N
authors.lastname: Shibui
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nagayasu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shirakawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000200:Action Potentials; D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000138:chemical synthesis / Q000633:toxicity*; D002186:Cannabinoids / Q000138:chemical synthesis / Q000633:toxicity*; D015198:Designer Drugs / Q000138:chemical synthesis / Q000633:toxicity*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism
chemical_list: D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D015198:Designer Drugs; D043884:Receptor, Cannabinoid, CB1; C000616976:5F-ADB cannabinoid