Prime

Type your tag names separated by a space and hit enter

Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze.

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.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • Publisher Full Text
  • 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

    ,

    Source

    Neuroscience letters 475:3 2010 May 21 pg 165-8

    MeSH

    Animals
    Anxiety
    Dronabinol
    Emotions
    Male
    Maze Learning
    Mice
    Mice, Inbred ICR
    Piperidines
    Psychotropic Drugs
    Pyrazoles
    Receptor, Cannabinoid, CB1
    Substance Withdrawal Syndrome

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    20363293

    Citation

    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 - 2010/1/22/received PY - 2010/3/10/revised PY - 2010/3/27/accepted PY - 2010/4/2/aheadofprint 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_SR141716_precipitated_delta9_tetrahydrocannabinol_withdrawal_in_mice_in_the_elevated_plus_maze_ L2 - http://linkinghub.elsevier.com/retrieve/pii/S0304-3940(10)00392-7 ER -