, Volume 234, Issue 14, pp 2207–2217 | Cite as

Effect of prior foot shock stress and Δ9-tetrahydrocannabinol, cannabidiolic acid, and cannabidiol on anxiety-like responding in the light-dark emergence test in rats

  • Erin M. Rock
  • Cheryl L. Limebeer
  • Gavin N. Petrie
  • Lauren A. Williams
  • Raphael Mechoulam
  • Linda A. ParkerEmail author
Original Investigation



Cannabis is commonly used by humans to relieve stress.

Objectives and methods

Here, we evaluate the potential of intraperitoneally (i.p.) administered Δ9-tetrahydrocannabiol (THC) and cannabidiolic acid (CBDA, the precursor of cannabidiol [CBD]) to produce dose-dependent effects on anxiety-like responding in the light-dark (LD) emergence test of anxiety-like responding in rats, when administered acutely or chronically (21 days). As well, we evaluate the potential of THC, CBDA, and CBD to reduce anxiogenic responding produced by foot shock (FS) stress 24 h prior to the LD test.


In the absence of the explicit FS stressor, THC (1 and 10 mg/kg) produced anxiogenic-like responding when administered acutely or chronically, but CBDA produced neither anxiogenic- nor anxiolytic-like responding. Administration of FS stress 24 h prior to the LD test enhanced anxiogenic-like responding (reduced time spent and increased latency to enter the light compartment) in rats pretreated with either vehicle (VEH) or THC (1 mg/kg); however, administration of CBDA (0.1–100 μg/kg) or CBD (5 mg/kg) prevented the FS-induced anxiogenic-like responding (an anxiolytic-like effect). The 5-hydroxytryptamine 1A (5-HT1A) receptor antagonist, WAY100635, reversed CBDA’s anxiolytic effect (1 μg/kg). Combining an anxiolytic dose of CBDA (1 μg/kg) or CBD (5 mg/kg) with an anxiogenic dose of THC (1 mg/kg) did not modify THC’s anxiogenic effect.


These results suggest the anxiolytic effects of CBDA and CBD may require the presence of a specific stressor.


Anxiety Anxiolytic Δ9-tetrahydrocannabiol Cannabidiolic acid Cannabidiol Foot shock Stress Light-dark emergence test Rat 



This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Collaborative Research and Development Grant (CRDPJ 476416-14) to LAP in partnership with Prairie Plant Systems Inc., as well as a grant to LAP from the NSERC (92056) and from Canadian Institute of Health Research (137122).

Compliance with ethical standards

All animal procedures complied with the Canadian Council on Animal Care and were approved by the Institutional Animal Care Committee (accredited by the Canadian Council on Animal Care).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Erin M. Rock
    • 1
  • Cheryl L. Limebeer
    • 1
  • Gavin N. Petrie
    • 1
  • Lauren A. Williams
    • 1
  • Raphael Mechoulam
    • 2
  • Linda A. Parker
    • 1
    Email author
  1. 1.Department of Psychology and Collaborative Neuroscience ProgramUniversity of GuelphGuelphCanada
  2. 2.Institute of Drug Research, School of Pharmacy Medical FacultyHebrew University of JerusalemJerusalemIsrael

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