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Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze.
Neurosci Lett 2010; 475(3):165-8NL

Abstract

Marijuana discontinuation has been recently reported to be anxiogenic in humans, which may predict relapse. Limited animal research has been carried out to model this withdrawal-associated negative affect. The current study sought to investigate the potential anxiety-like effects of cannabinoid withdrawal in mice. Male ICR mice were injected s.c. with delta9-tetrahydrocannabinol (THC) at 10mg/kg or vehicle once daily for 10 days. To precipitate withdrawal, the cannabinoid CB1 antagonist SR141716 (0.3, 1.0, or 3.0mg/kg) or vehicle was administrated i.p. 4h following the last THC or vehicle treatment. Thirty minutes later, mice were tested on the elevated plus-maze (EPM) for 5min. SR141716 did not significantly change EPM behaviors in vehicle-treated mice. In contrast, SR141716 precipitated a reduction in exploration of the open arms of EPM in mice repeatedly treated with THC vs vehicle. At 3.0mg/kg, SR141716 significantly reduced % open arm entries of the total arm entries, % open arm time of total time in arms, and the absolute time spent in open arms. No significant differences in the number of closed or total arm entries were observed, indicating that the behavioral changes were not due to altered motor activity. Collectively, the present results constitute the first evidence that cannabinoid withdrawal produces anxiety-like effects in mice. This animal model may help to identify the mechanisms that contribute to adaptations in the neuronal circuitry of the brain that are expressed as emotional symptoms of cannabinoid withdrawal.

Authors+Show Affiliations

Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, 3420 N Broad St, Philadelphia, PA 19140, USA. phuang@temple.edu

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20363293

Citation

Huang, Peng, et al. "Anxiety-like Effects of SR141716-precipitated Delta9-tetrahydrocannabinol Withdrawal in Mice in the Elevated Plus-maze." Neuroscience Letters, vol. 475, no. 3, 2010, pp. 165-8.
Huang P, Liu-Chen LY, Kirby LG. Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze. Neurosci Lett. 2010;475(3):165-8.
Huang, P., Liu-Chen, L. Y., & Kirby, L. G. (2010). Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze. Neuroscience Letters, 475(3), pp. 165-8. doi:10.1016/j.neulet.2010.03.071.
Huang P, Liu-Chen LY, Kirby LG. Anxiety-like Effects of SR141716-precipitated Delta9-tetrahydrocannabinol Withdrawal in Mice in the Elevated Plus-maze. Neurosci Lett. 2010 May 21;475(3):165-8. PubMed PMID: 20363293.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze. AU - Huang,Peng, AU - Liu-Chen,Lee-Yuan, AU - Kirby,Lynn G, Y1 - 2010/04/02/ PY - 2010/01/22/received PY - 2010/03/10/revised PY - 2010/03/27/accepted PY - 2010/4/6/entrez PY - 2010/4/7/pubmed PY - 2010/7/1/medline SP - 165 EP - 8 JF - Neuroscience letters JO - Neurosci. Lett. VL - 475 IS - 3 N2 - Marijuana discontinuation has been recently reported to be anxiogenic in humans, which may predict relapse. Limited animal research has been carried out to model this withdrawal-associated negative affect. The current study sought to investigate the potential anxiety-like effects of cannabinoid withdrawal in mice. Male ICR mice were injected s.c. with delta9-tetrahydrocannabinol (THC) at 10mg/kg or vehicle once daily for 10 days. To precipitate withdrawal, the cannabinoid CB1 antagonist SR141716 (0.3, 1.0, or 3.0mg/kg) or vehicle was administrated i.p. 4h following the last THC or vehicle treatment. Thirty minutes later, mice were tested on the elevated plus-maze (EPM) for 5min. SR141716 did not significantly change EPM behaviors in vehicle-treated mice. In contrast, SR141716 precipitated a reduction in exploration of the open arms of EPM in mice repeatedly treated with THC vs vehicle. At 3.0mg/kg, SR141716 significantly reduced % open arm entries of the total arm entries, % open arm time of total time in arms, and the absolute time spent in open arms. No significant differences in the number of closed or total arm entries were observed, indicating that the behavioral changes were not due to altered motor activity. Collectively, the present results constitute the first evidence that cannabinoid withdrawal produces anxiety-like effects in mice. This animal model may help to identify the mechanisms that contribute to adaptations in the neuronal circuitry of the brain that are expressed as emotional symptoms of cannabinoid withdrawal. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/20363293/abstract/Anxiety_like_effects_of_SR141 L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(10)00392-7 DB - PRIME DP - Unbound Medicine ER -