title: Synthetic cannabinoid JWH-018 and its halogenated derivatives JWH-018-Cl and JWH-018-Br impair Novel Object Recognition in mice: Behavioral, electrophysiological and neurochemical evidence.
abstract: It is well known that an impairment of learning and memory function is one of the major physiological effects caused by natural or synthetic cannabinoid consumption in rodents, nonhuman primates and in humans. JWH-018 and its halogenated derivatives (JWH-018-Cl and JWH-018-Br) are synthetic CB1/CB2 cannabinoid agonists, illegally marketed as "Spice" and "herbal blend" for their Cannabis-like psychoactive effects. In the present study the effects of acute exposure to JWH-018, JWH-018-Cl, JWH-018-Br (JWH-018-R compounds) and Δ(9)-THC (for comparison) on Novel Object Recognition test (NOR) has been investigated in mice. Moreover, to better characterize the effects of JWH-018-R compounds on memory function, in vitro electrophysiological and neurochemical studies in hippocampal preparations have been performed. JWH-018, JWH-018-Cl and JWH-018-Br dose-dependently impaired both short- and long-memory retention in mice (respectively 2 and 24 h after training session). Their effects resulted more potent respect to that evoked by Δ(9)-THC. Moreover, in vitro studies showed as JWH-018-R compounds negatively affected electrically evoked synaptic transmission, LTP and aminoacid (glutamate and GABA) release in hippocampal slices. Behavioral, electrophysiological and neurochemical effects were fully prevented by CB1 receptor antagonist AM251 pretreatment, suggesting a CB1 receptor involvement. These data support the hypothesis that synthetic JWH-018-R compounds, as Δ(9)-THC, impair cognitive function in mice by interfering with hippocampal synaptic transmission and memory mechanisms. This data outline the danger that the use and/or abuse of these synthetic cannabinoids may represent for the cognitive process in human consumer.
authors.affiliation: Department of Medical Sciences, University of Ferrara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Barbieri
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ossato
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Canazza
authors.affiliation: Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Trapella
authors.affiliation: Department of Medical Sciences, University of Ferrara, Italy.
authors.forename: A C
authors.initials: AC
authors.lastname: Borelli
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Beggiato
authors.affiliation: Department of Public Health and Community Medicine, University of Verona, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Rimondo
authors.affiliation: U.R.I.To.N., Forensic Toxicology Unit, Department of Health Science, University of Florence, Florence, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Serpelloni
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ferraro
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, Italy; Center for Neuroscience and Istituto Nazionale di Neuroscienze, Italy. Electronic address: m.marti@unife.it.
authors.forename: M
authors.initials: M
authors.lastname: Marti
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena / Q000187:drug effects* / Q000502:physiology; D054879:Halogenation; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology*; D009924:Organ Culture Techniques; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000502:physiology; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology
chemical_list: C000605613:1-(5-bromopentyl)-3-(1-naphthoyl)indole; C000605612:1-(5-chloropentyl)-3-(1-naphthoyl)indole; D007211:Indoles; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C552597:1-pentyl-3-(1-naphthoyl)indole
keywords: AM251 (PubChem CID: 2125); GABA/glutamate release; Hippocampus; JWH-018; JWH-018 (PubChem CID: 10382701); JWH-018-Br (PubChem CID: 91740913); JWH-018-Cl (PubChem CID: 91713116); LTP; Novel object recognition; Δ(9)-THC (PubChem CID: 16078)