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Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors.

Abstract

Activation of 5-HT1A receptors in the dorsal periaqueductal gray (dPAG) impairs escape behavior, suggesting a panicolytic-like effect. Cannabidiol (CBD), a major non-psychotomimetic compound present in Cannabis sativa, causes anxiolytic-like effects after intra-dPAG microinjections by activating 5-HT1A receptors. In the present work we tested the hypothesis that CBD could also impair escape responses evoked by two proposed animal models of panic: the elevated T-maze (ETM) and electric stimulation of dPAG. In experiment 1 male Wistar rats with a single cannula implanted in the dPAG received a microinjection of CBD or vehicle and, 10 min later, were submitted to the ETM and open field tests. In experiment 2 escape electrical threshold was measured in rats with chemitrodes implanted in the dPAG before and 10 min after CBD microinjection. In experiment 3 similar to experiment 2 except that the animals received a previous intra-dPAG administration of WAY-100635, a 5-HT1A receptor antagonist, before CBD treatment. In the ETM microinjection of CBD into the dPAG impaired inhibitory avoidance acquisition, an anxiolytic-like effect, and inhibited escape response, a panicolytic-like effect. The drug also increased escape electrical threshold, an effect that was prevented by WAY-100635. Together, the results suggest that CBD causes panicolytic effects in the dPAG by activating 5-HT1A receptors.

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  • Authors+Show Affiliations

    ,

    Neuroscience and Behavioral Sciences, School of Medicine of Ribeirão Preto, Campus USP, Ribeirão Preto, SP, Brazil. vanpaso@cb.ufrn.br

    , , , ,

    Source

    Behavioural brain research 213:2 2010 Dec 1 pg 225-9

    MeSH

    Animals
    Cannabidiol
    Electric Stimulation
    Male
    Maze Learning
    Microinjections
    Models, Animal
    Panic
    Periaqueductal Gray
    Piperazines
    Pyridines
    Rats
    Rats, Wistar
    Serotonin 5-HT1 Receptor Agonists
    Serotonin 5-HT1 Receptor Antagonists

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    20457188

    Citation

    TY - JOUR T1 - Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors. AU - Soares,Vanessa de Paula, AU - Campos,Alline Cristina, AU - Bortoli,Valquíria Camin de, AU - Zangrossi,Hélio,Jr AU - Guimarães,Francisco Silveira, AU - Zuardi,Antonio Waldo, Y1 - 2010/05/08/ PY - 2010/3/25/received PY - 2010/4/27/revised PY - 2010/5/1/accepted PY - 2010/5/8/aheadofprint PY - 2010/5/12/entrez PY - 2010/5/12/pubmed PY - 2010/10/20/medline SP - 225 EP - 9 JF - Behavioural brain research JO - Behav. Brain Res. VL - 213 IS - 2 N2 - Activation of 5-HT1A receptors in the dorsal periaqueductal gray (dPAG) impairs escape behavior, suggesting a panicolytic-like effect. Cannabidiol (CBD), a major non-psychotomimetic compound present in Cannabis sativa, causes anxiolytic-like effects after intra-dPAG microinjections by activating 5-HT1A receptors. In the present work we tested the hypothesis that CBD could also impair escape responses evoked by two proposed animal models of panic: the elevated T-maze (ETM) and electric stimulation of dPAG. In experiment 1 male Wistar rats with a single cannula implanted in the dPAG received a microinjection of CBD or vehicle and, 10 min later, were submitted to the ETM and open field tests. In experiment 2 escape electrical threshold was measured in rats with chemitrodes implanted in the dPAG before and 10 min after CBD microinjection. In experiment 3 similar to experiment 2 except that the animals received a previous intra-dPAG administration of WAY-100635, a 5-HT1A receptor antagonist, before CBD treatment. In the ETM microinjection of CBD into the dPAG impaired inhibitory avoidance acquisition, an anxiolytic-like effect, and inhibited escape response, a panicolytic-like effect. The drug also increased escape electrical threshold, an effect that was prevented by WAY-100635. Together, the results suggest that CBD causes panicolytic effects in the dPAG by activating 5-HT1A receptors. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/20457188/abstract/Intra_dorsal_periaqueductal_gray_administration_of_cannabidiol_blocks_panic_like_response_by_activating_5_HT1A_receptors_ L2 - http://linkinghub.elsevier.com/retrieve/pii/S0166-4328(10)00343-8 ER -