title: JWH-018 impairs sensorimotor functions in mice.
abstract: Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) is a synthetic cannabinoid agonist illegally marketed in "Spice" and "herbal blend" for its psychoactive effect greater than those produced by cannabis. In rodents JWH-018 reproduces typical effects of (-)-Δ(9)-THC or Dronabinol® (Δ(9)-THC) such as hypothermia, analgesia, hypolocomotion and akinesia, while its effects on sensorimotor functions are still unknown. Therefore, the aim of the present study is to investigate the effect of acute administration of JWH-018 (0.01-6mg/kg i.p.) on sensorimotor functions in male CD-1 mice and to compare its effects with those caused by the administration of Δ(9)-THC (0.01-6mg/kg i.p.). A specific battery of behavioral tests were adopted to investigate effects of cannabinoid agonists on sensorimotor functions (visual, auditory, tactile) and neurological changes (convulsion, myoclonia, hyperreflexia) while video-tracking analysis was used to study spontaneous locomotion. JWH-018 administration inhibited sensorimotor responses at lower doses (0.01-0.1mg/kg), reduced spontaneous locomotion at intermediate/high doses (1-6mg/kg) and induced convulsions, myoclonia and hyperreflexia at high doses (6mg/kg). Similarly, administration of Δ(9)-THC reduced sensorimotor responses in mice but it did not inhibit spontaneous locomotion and it did not induce neurological alterations. All behavioral effects and neurological alterations were prevented by the administration of the selective CB1 receptor antagonist/inverse agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (AM 251). For the first time these data demonstrate that JWH-018 impairs sensorimotor responses in mice. This aspect should be carefully evaluated to better understand the potential danger that JWH-018 may pose to public health, with particular reference to decreased performance in driving and hazardous works.
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: A
authors.initials: A
authors.lastname: Vigolo
authors.affiliation: Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Trapella
authors.affiliation: Italian National Early Warning System, Drug Policies Department, Presidency of the Council of Ministers, Verona Coordination Unit, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Seri
authors.affiliation: Italian National Early Warning System, Drug Policies Department, Presidency of the Council of Ministers, Verona Coordination Unit, Italy; Department of Public Health and Community Medicine, University of Verona, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Rimondo
authors.affiliation: Italian National Early Warning System, Drug Policies Department, Presidency of the Council of Ministers, Verona Coordination Unit, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Serpelloni
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; D063386:Cannabinoid Receptor Agonists / Q000633:toxicity*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D003315:Cornea; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000633:toxicity; D054644:Ear Auricle; D006309:Hearing / Q000187:drug effects; D013287:Illicit Drugs / Q000633:toxicity*; D007211:Indoles / Q000633:toxicity*; D008297:Male; D051379:Mice; D009068:Movement / Q000187:drug effects; D009281:Naphthalenes / Q000633:toxicity*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D014110:Touch / Q000187:drug effects; D014738:Vibrissae; D014741:Video Recording; D014785:Vision, Ocular / Q000187:drug effects
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D013287:Illicit Drugs; D007211:Indoles; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D013759:Dronabinol; C552597:1-pentyl-3-(1-naphthoyl)indole
keywords: AM 251; JWH-018; sensorimotor responses; spontaneous locomotion; synthetic cannabinoids; Δ(9)-THC