Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze.
Peng Huang, Lee-Yuan Liu-Chen, Lynn G Kirby
Neuroscience Letters May 21, 2010 DOI: 10.1016/j.neulet.2010.03.071 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Male ICR mice |
| Interventions | delta9-tetrahydrocannabinol (THC) SR141716 |
| Dose | THC 10 mg/kg; SR141716 0.3, 1.0, or 3.0 mg/kg |
| Duration | 10 days of daily THC or vehicle treatment; SR141716 given 4 hours after the last treatment; elevated plus-maze testing 30 minutes later for 5 minutes |
| Measures | elevated plus-maze (EPM) |
| Topics | Anxiety Cannabis |
| Key findings | In mice treated repeatedly with THC, the CB1 antagonist SR141716 precipitated anxiety-like behavior, reducing open-arm exploration on the elevated plus-maze at 3.0 mg/kg without affecting closed or total arm entries. The authors state this is the first evidence that cannabinoid withdrawal produces anxiety-like effects in mice, offering a model for studying the emotional symptoms of withdrawal. |
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.
Comparable studies
Other preclinical and animal studies on cannabis for anxiety, most cited first.
Citations in the library
Cited by 3
- Single and combined effects of plant-derived and synthetic cannabinoids on cognition and cannabinoid-associated withdrawal signs in mice. British Journal of Pharmacology May 2019
- Novel behavioral assays of spontaneous and precipitated THC withdrawal in mice. Drug and Alcohol Dependence October 1, 2018
- Marijuana dependence: not just smoke and mirrors. ILAR Journal 2011
Cites 2
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- Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. Journal of Pharmacology and Experimental Therapeutics July 2006