{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T11:50:44Z","timestamp":1774698644153,"version":"3.50.1"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2&3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:p>Although the behavioral effects of acute and chronic exposure to cannabinoids have been extensively studied in mice, spontaneous withdrawal following exposure to cannabinoids has not been well characterized in this species. To address this issue, different groups of mice were treated for 5 days with saline, 20\u201336 mg\/kg\/day of the CB partial agonist \u0394<jats:sup>9<\/jats:sup>-tetrahydrocannabinol (\u0394<jats:sup>9<\/jats:sup>-THC), or 0.06\u20130.1 mg\/kg\/day of the CB high-efficacy agonist AM2389. Initial studies assessed changes in observable behavior (paw tremors) that were scored from the recordings taken at 4 or 24 h after the last injection. Subsequently, radiotelemetry was used to continuously measure body temperature and locomotor activity before (baseline), during, and after the 5-day dosing regimens. Results show that increases in paw tremors occurred following 5-day exposure to AM2389 or \u0394<jats:sup>9<\/jats:sup>-THC. In telemetry studies, acute AM2389 or THC decreased both temperature and activity. Rapid tolerance occurred to the hypothermic effects of the cannabinoids, whereas locomotor activity continued to be suppressed following each drug injection. In contrast, increases in locomotor activity were evident 12\u201372 h after discontinuing daily injections of either 0.06 or 0.1 mg\/kg\/day AM2389. Increases in locomotor activity were also noted in mice treated daily with 30 or 36, but not 20 mg\/kg\/day \u0394<jats:sup>9<\/jats:sup>-THC; these effects were smaller and appeared later than effects seen in AM2389-treated mice. These results indicate that the discontinuation of daily treatment with a CB high-efficacy agonist will yield evidence of spontaneous withdrawal that may reflect prior dependence, and that the degree of cannabinoid dependence may vary in relation to the dose or efficacy of the agonist injected daily.<\/jats:p>","DOI":"10.1097\/fbp.0000000000000665","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T11:35:06Z","timestamp":1639568106000},"page":"184-194","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":10,"title":["Evidence for spontaneous cannabinoid withdrawal in mice"],"prefix":"10.1097","volume":"33","author":[{"given":"Carol","family":"Paronis","sequence":"first","affiliation":[{"name":"Laboratory of Preclinical Pharmacology, McLean Hospital"},{"name":"Department of Pharmaceutical Sciences"},{"name":"Center for Drug Discovery, Northeastern University, Belmont, Massachusetts, 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