Precipitated Δ9-THC withdrawal reduces motivation for sucrose reinforcement in mice.

Autor: Eckard ML; Department of Psychology, West Virginia University, Morgantown, WV, USA; Department of Environmental Medicine, University of Rochester, Rochester, NY, USA. Electronic address: Matthew_Eckard@URMC.Rochester.edu., Trexler KR; Department of Psychology, West Virginia University, Morgantown, WV, USA., Kotson BT; Department of Psychology, West Virginia University, Morgantown, WV, USA., Anderson KG; Department of Psychology, West Virginia University, Morgantown, WV, USA; Department of Neuroscience, West Virginia University, Morgantown, USA., Kinsey SG; Department of Psychology, West Virginia University, Morgantown, WV, USA; Department of Neuroscience, West Virginia University, Morgantown, USA; School of Nursing, University of Connecticut, Storrs, CT, USA.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2020 Aug; Vol. 195, pp. 172966. Date of Electronic Publication: 2020 Jun 09.
DOI: 10.1016/j.pbb.2020.172966
Abstrakt: Withdrawal from Δ 9 -tetrahyrocannibidol (THC) is associated with a host of dysphoric symptoms that increase probability of relapse. To date, many animal models of THC withdrawal rely on withdrawal-induced somatic withdrawal signs leaving withdrawal-suppressed behavior relatively unexplored. As compared with withdrawal-induced behaviors, ongoing behavior that is suppressed by withdrawal is a useful behavioral endpoint because it 1) more effectively models the subjective aspects of withdrawal and 2) identifies pharmacotherapies that restore behavior to baseline levels, rather than eliminate behavior induced by withdrawal. The current study assessed effects of spontaneous and rimonabant-precipitated THC withdrawal in mice responding on a progressive-ratio (PR) schedule of sucrose water reinforcement. Once behavior stabilized, male and female mice were administered THC (10 mg/kg, s.c.) or vehicle for five or six days. THC was either discontinued and behavior monitored for three days during abstinence, or the CB 1 antagonist rimonabant (2 mg/kg, i.p.) was used to precipitate withdrawal. Whereas spontaneous THC withdrawal had no effect on PR performance, THC-treated mice were differentially sensitive to rimonabant administration via large decreases in break point, overall response rate, and run rate relative to vehicle-treated mice. Importantly, pretreatment with the CB 1 positive allosteric modulator ZCZ011 (10 mg/kg, i.p.) did not prevent precipitated-withdrawal-induced behavioral impairment. These extend findings of earlier studies suggesting operant baselines are useful tools to study subjective effects of cannabinoid withdrawal. Additionally, operant baselines allow withdrawal pharmacotherapies to be tested in a restoration-of-function context, which may be more sensitive, selective, and clinically relevant.
Competing Interests: Declaration of competing interest None.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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