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Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats.

Abstract

RATIONALE

Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal periaqueductal gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood.

OBJECTIVE

The present study evaluates the role of the serotonergic neurotransmission within the DPAG in the modulation of escape responses of rats chronically treated with CBD.

METHODS

Male Wistar rats received acute or repeated (5 mg/Kg/daily/21 days) administration of CBD and were submitted to the elevated T-maze (ETM). We also investigated if CBD effects on the ETM depend on facilitation of 5-HT1A-mediated neurotransmission in the DPAG. To this latter aim, we verified if these effects would be prevented by intra-DPAG injection of the 5-HT1A receptor antagonist WAY100635 (0.37 nmol/0.2 μL). Also, we verified, by in vivo microdialysis, if CBD chronic treatment increases serotonin (5-HT) release and, by quantitative polymerase chain reaction, if there are changes in 5HT-1A or 5HT-2C mRNA expression in DPAG.

RESULTS

The results showed that repeated but not acute peripheral administration of CBD decreases escape responses in the ETM, suggesting a panicolytic effect. This treatment did not change 5HT-1A or 5-HT-2C receptor mRNA expression nor modify serotonin extracellular concentrations in the DPAG. CBD effects were prevented by DPAG injection of the 5-HT1A receptor antagonist.

CONCLUSIONS

Together, these findings suggest that repeated treatment with CBD induces anti-panic effects by acting on 5-HT1A receptors in DPAG.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 3900 Bandeirantes av., Monte Alegre, Ribeirão Preto, São Paulo, Brazil. allinecampos@usp.br

    , , , , , , ,

    Source

    Psychopharmacology 226:1 2013 Mar pg 13-24

    MeSH

    Animals
    Behavior, Animal
    Brain Mapping
    Cannabidiol
    Dose-Response Relationship, Drug
    Male
    Maze Learning
    Microdialysis
    Panic Disorder
    Periaqueductal Gray
    Polymerase Chain Reaction
    Rats, Wistar
    Receptor, Serotonin, 5-HT1A
    Serotonin
    Synaptic Transmission

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    23007604

    Citation

    Campos, Alline Cristina, et al. "Involvement of Serotonin-mediated Neurotransmission in the Dorsal Periaqueductal Gray Matter On Cannabidiol Chronic Effects in Panic-like Responses in Rats." Psychopharmacology, vol. 226, no. 1, 2013, pp. 13-24.
    Campos AC, de Paula Soares V, Carvalho MC, et al. Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats. Psychopharmacology (Berl). 2013;226(1):13-24.
    Campos, A. C., de Paula Soares, V., Carvalho, M. C., Ferreira, F. R., Vicente, M. A., Brandão, M. L., ... Guimarães, F. S. (2013). Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats. Psychopharmacology, 226(1), pp. 13-24. doi:10.1007/s00213-012-2878-7.
    Campos AC, et al. Involvement of Serotonin-mediated Neurotransmission in the Dorsal Periaqueductal Gray Matter On Cannabidiol Chronic Effects in Panic-like Responses in Rats. Psychopharmacology (Berl). 2013;226(1):13-24. PubMed PMID: 23007604.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats. AU - Campos,Alline Cristina, AU - de Paula Soares,Vanessa, AU - Carvalho,Milene C, AU - Ferreira,Frederico Rogerio, AU - Vicente,Maria Adrielle, AU - Brandão,Marcus Lira, AU - Zuardi,Antonio Waldo, AU - Zangrossi,Hélio,Jr AU - Guimarães,Francisco Silveira, Y1 - 2012/09/25/ PY - 2012/05/08/received PY - 2012/09/06/accepted PY - 2012/9/26/entrez PY - 2012/9/26/pubmed PY - 2013/7/31/medline SP - 13 EP - 24 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 226 IS - 1 N2 - RATIONALE: Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal periaqueductal gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood. OBJECTIVE: The present study evaluates the role of the serotonergic neurotransmission within the DPAG in the modulation of escape responses of rats chronically treated with CBD. METHODS: Male Wistar rats received acute or repeated (5 mg/Kg/daily/21 days) administration of CBD and were submitted to the elevated T-maze (ETM). We also investigated if CBD effects on the ETM depend on facilitation of 5-HT1A-mediated neurotransmission in the DPAG. To this latter aim, we verified if these effects would be prevented by intra-DPAG injection of the 5-HT1A receptor antagonist WAY100635 (0.37 nmol/0.2 μL). Also, we verified, by in vivo microdialysis, if CBD chronic treatment increases serotonin (5-HT) release and, by quantitative polymerase chain reaction, if there are changes in 5HT-1A or 5HT-2C mRNA expression in DPAG. RESULTS: The results showed that repeated but not acute peripheral administration of CBD decreases escape responses in the ETM, suggesting a panicolytic effect. This treatment did not change 5HT-1A or 5-HT-2C receptor mRNA expression nor modify serotonin extracellular concentrations in the DPAG. CBD effects were prevented by DPAG injection of the 5-HT1A receptor antagonist. CONCLUSIONS: Together, these findings suggest that repeated treatment with CBD induces anti-panic effects by acting on 5-HT1A receptors in DPAG. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/23007604/Involvement_of_serotonin_mediated_neurotransmission_in_the_dorsal_periaqueductal_gray_matter_on_cannabidiol_chronic_effects_in_panic_like_responses_in_rats_ L2 - https://dx.doi.org/10.1007/s00213-012-2878-7 DB - PRIME DP - Unbound Medicine ER -