Kristen R Trexler1, Sara R Nass2, Molly S Crowe3, Joshua D Gross4, Margaret S Jones1, Austin W McKitrick1, David P Siderovski4, Steven G Kinsey5. 1. Department of Psychology, West Virginia University, 1124 Life Sciences Building, P.O. Box 6040, Morgantown, WV 26506-6040, USA. 2. Department of Psychology, West Virginia University, 1124 Life Sciences Building, P.O. Box 6040, Morgantown, WV 26506-6040, USA; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, 1112 East Clay Street, McGuire Hall, Box 980613, Richmond, VA 23298-0524, USA. 3. Department of Psychology, West Virginia University, 1124 Life Sciences Building, P.O. Box 6040, Morgantown, WV 26506-6040, USA; Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, 1101 East Marshall Street, Box 980551, Richmond, VA 23298-0551, USA. 4. Department of Physiology, Pharmacology and Neuroscience, West Virginia University School of Medicine, P.O. Box 9229, Health Sciences North Morgantown, WV 26506-9229, USA. 5. Department of Psychology, West Virginia University, 1124 Life Sciences Building, P.O. Box 6040, Morgantown, WV 26506-6040, USA. Electronic address: sgkinsey@mail.wvu.edu.
Abstract
BACKGROUND: A subset of cannabis users develop some degree of Cannabis Use Disorder (CUD). Although behavioral therapy has some success in treating CUD, many users relapse, often citing altered sleep, mood, and irritability. Preclinical animal tests of cannabinoid withdrawal focus primarily on somatic-related behaviors precipitated by a cannabinoid receptor antagonist. The goal of the present study was to develop novel cannabinoid withdrawal assays that are either antagonist-precipitated or spontaneously induced by abstinence. METHODS: C57BL/6 J mice were repeatedly administered the phytocannabinoid Δ9-tetrahydrocannabinol (THC; 1, 10 or 50 mg/kg, s.c.), the synthetic cannabinoid receptor agonist JWH-018 (1 mg/kg, s.c.), or vehicle (1:1:18 parts ethanol:Kolliphor EL:saline, s.c.) for 6 days. Withdrawal was precipitated with the cannabinoid receptor inverse agonist rimonabant (3 mg/kg, i.p.) or elicited via abstinence (i.e., spontaneous withdrawal), and putative stress-related behavior was scored. Classic somatic signs of cannabinoid withdrawal were also quantified. RESULTS: Precipitated THC withdrawal significantly increased plasma corticosterone. Precipitated withdrawal from either THC or JWH-018 suppressed marble burying, increased struggling in the tail suspension test, and elicited somatic withdrawal behaviors. The monoacylglycerol lipase inhibitor JZL184 attenuated somatic precipitated withdrawal but had no effect on marble burying or struggling. Spontaneous THC or JWH-018 withdrawal-induced paw tremors, head twitches, and struggled in the tail suspension test after 24-48 h abstinence. JZL184 or THC attenuated these spontaneous withdrawal-induced behaviors. CONCLUSION: Outcomes from tail suspension and marble burying tests reveal that THC withdrawal is multifaceted, eliciting and suppressing behaviors in these tests, in addition to inducing well-documented somatic signs of withdrawal.
BACKGROUND: A subset of cannabis users develop some degree of Cannabis Use Disorder (CUD). Although behavioral therapy has some success in treating CUD, many users relapse, often citing altered sleep, mood, and irritability. Preclinical animal tests of cannabinoid withdrawal focus primarily on somatic-related behaviors precipitated by a cannabinoid receptor antagonist. The goal of the present study was to develop novel cannabinoid withdrawal assays that are either antagonist-precipitated or spontaneously induced by abstinence. METHODS: C57BL/6 J mice were repeatedly administered the phytocannabinoid Δ9-tetrahydrocannabinol (THC; 1, 10 or 50 mg/kg, s.c.), the synthetic cannabinoid receptor agonist JWH-018 (1 mg/kg, s.c.), or vehicle (1:1:18 parts ethanol:Kolliphor EL:saline, s.c.) for 6 days. Withdrawal was precipitated with the cannabinoid receptor inverse agonist rimonabant (3 mg/kg, i.p.) or elicited via abstinence (i.e., spontaneous withdrawal), and putative stress-related behavior was scored. Classic somatic signs of cannabinoid withdrawal were also quantified. RESULTS: Precipitated THC withdrawal significantly increased plasma corticosterone. Precipitated withdrawal from either THC or JWH-018 suppressed marble burying, increased struggling in the tail suspension test, and elicited somatic withdrawal behaviors. The monoacylglycerol lipase inhibitor JZL184 attenuated somatic precipitated withdrawal but had no effect on marble burying or struggling. Spontaneous THC or JWH-018 withdrawal-induced paw tremors, head twitches, and struggled in the tail suspension test after 24-48 h abstinence. JZL184 or THC attenuated these spontaneous withdrawal-induced behaviors. CONCLUSION: Outcomes from tail suspension and marble burying tests reveal that THC withdrawal is multifaceted, eliciting and suppressing behaviors in these tests, in addition to inducing well-documented somatic signs of withdrawal.
Authors: Wynne Q Zhang; Corey M Smolik; Priscilla A Barba-Escobedo; Monica Gamez; Jesus J Sanchez; Martin A Javors; Lynette C Daws; Georgianna G Gould Journal: Neuropharmacology Date: 2014-11-04 Impact factor: 5.250
Authors: Heather N Richardson; Yu Zhao; Eva M Fekete; Cindy K Funk; Peter Wirsching; Kim D Janda; Eric P Zorrilla; George F Koob Journal: Pharmacol Biochem Behav Date: 2007-10-23 Impact factor: 3.533
Authors: Carol Paronis; Christos Iliopoulos-Tsoutsouvas; Ioannis Papanastasiou; Alex Makriyannis; Jack Bergman; Spyros P Nikas Journal: Behav Pharmacol Date: 2022-04-01 Impact factor: 2.293
Authors: Attilio Iemolo; Patricia Montilla-Perez; Jacques Nguyen; Victoria B Risbrough; Michael A Taffe; Francesca Telese Journal: Neuropharmacology Date: 2021-02-11 Impact factor: 5.250
Authors: Andrew J Kesner; Yolanda Mateo; Karina P Abrahao; Stephanie Ramos-Maciel; Matthew J Pava; Alexa L Gracias; Riley T Paulsen; Hartley B Carlson; David M Lovinger Journal: Neuropsychopharmacology Date: 2022-04-27 Impact factor: 8.294