JWH-018 IMPAIRS SENSORIMOTOR FUNCTIONS IN MICE

被引:63
作者
Ossato, A. [1 ]
Vigolo, A. [1 ]
Trapella, C. [4 ]
Seri, C. [5 ]
Rimondo, C. [5 ,6 ]
Serpelloni, G. [5 ]
Marti, M. [1 ,2 ,3 ]
机构
[1] Univ Ferrara, Dept Life Sci & Biotechnol SVeB, I-44121 Ferrara, Italy
[2] Ctr Neurosci, Padua, Italy
[3] Ist Nazl Neurosci, Padua, Italy
[4] Univ Ferrara, Dept Chem & Pharmaceut Sci, I-44100 Ferrara, Italy
[5] Italian Natl Early Warning Syst, Presidency Council Ministers, Drug Policies Dept, Verona Coordinat Unit, Milan, Italy
[6] Univ Verona, Dept Publ Hlth & Community Med, I-37100 Verona, Italy
关键词
AM; 251; JWH-018; Delta(9)-THC; sensorimotor responses; synthetic cannabinoids; spontaneous locomotion; DORSAL COCHLEAR NUCLEUS; CANNABINOID RECEPTOR AGONIST; PRIMARY SOMATOSENSORY CORTEX; BINOCULAR DEPTH INVERSION; ACOUSTIC STARTLE REFLEX; MOUSE VISUAL-CORTEX; SYNTHETIC CANNABINOIDS; CB1; RECEPTORS; MULTISENSORY INTEGRATION; SAFETY PHARMACOLOGY;
D O I
10.1016/j.neuroscience.2015.05.021
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 (-)-Delta(9)-THC or Dronabinol (R) (Delta(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 (0.01-6 mg/kg i.p.) on sensorimotor functions in male CD-1 mice and to compare its effects with those caused by the administration of Delta(9)-THC (0.01-6 mg/kg i.p.). Aspecific 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 (0.01-0.1 mg/kg), reduced spontaneous locomotion at intermediate/high doses (1-6 mg/kg) and induced convulsions, myoclonia and hyperreflexia at high doses (6 mg/kg). Similarly, administration of Delta(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-iodophe nyl)-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. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:174 / 188
页数:15
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