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Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats.

Abstract

RATIONALE

Systemic administration of cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is able to attenuate cardiovascular and behavioral (freezing) changes induced by re-exposure to a context that had been previously paired with footshocks. The brain sites mediating this effect, however, remain unknown. The medial prefrontal cortex (mPFC) has been related to contextual fear conditioning.

OBJECTIVES

(1) To verify, using c-Fos immunocytochemistry, if the mPFC is involved in the attenuation of contextual fear induced by systemic administration of CBD; (2) to investigate if direct microinjections of CBD into mPFC regions would also attenuate contextual fear.

RESULTS

Confirming previous results systemic administration of CBD (10mg/kg) decreased contextual fear and associated c-Fos expression in the prefrontal cortex (prelimbic and infralimbic regions). The drug also attenuated c-Fos expression in the bed nucleus of the stria terminalis (BNST). Direct CBD (30 nmol) microinjection into the PL prefrontal cortex reduced freezing induced by re-exposure to the aversively conditioned context. In the infralimbic (IL) prefrontal cortex, however, CBD (30 nmol) produced an opposite result, increasing the expression of contextual fear conditioning. This result was confirmed by an additional experiment where the conditioning session was performed under a less aversive protocol.

CONCLUSION

These results suggest that the PL prefrontal cortex may be involved in the attenuation of contextual fear induced by systemic injection of CBD. They also support the proposition that the IL and PL play opposite roles in fear conditioning. A possible involvement of the BNST in CBD effects needs to be further investigated.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Pharmacology, School of Medicine of Ribeirão Preto, Campus USP, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, SP, Brazil.

    ,

    Source

    Behavioural brain research 207:1 2010 Feb 11 pg 105-11

    MeSH

    Animals
    Behavior, Animal
    Cannabidiol
    Conditioning, Classical
    Dose-Response Relationship, Drug
    Electroshock
    Exploratory Behavior
    Fear
    Hypothalamus
    Immunohistochemistry
    Male
    Neurons
    Prefrontal Cortex
    Proto-Oncogene Proteins c-fos
    Rats
    Rats, Wistar
    Spatial Behavior

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    19800921

    Citation

    Lemos, José Inácio, et al. "Involvement of the Prelimbic Prefrontal Cortex On Cannabidiol-induced Attenuation of Contextual Conditioned Fear in Rats." Behavioural Brain Research, vol. 207, no. 1, 2010, pp. 105-11.
    Lemos JI, Resstel LB, Guimarães FS. Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats. Behav Brain Res. 2010;207(1):105-11.
    Lemos, J. I., Resstel, L. B., & Guimarães, F. S. (2010). Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats. Behavioural Brain Research, 207(1), pp. 105-11. doi:10.1016/j.bbr.2009.09.045.
    Lemos JI, Resstel LB, Guimarães FS. Involvement of the Prelimbic Prefrontal Cortex On Cannabidiol-induced Attenuation of Contextual Conditioned Fear in Rats. Behav Brain Res. 2010 Feb 11;207(1):105-11. PubMed PMID: 19800921.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats. AU - Lemos,José Inácio, AU - Resstel,Leonardo Barbosa, AU - Guimarães,Francisco Silveira, Y1 - 2009/10/02/ PY - 2009/08/31/received PY - 2009/09/21/revised PY - 2009/09/25/accepted PY - 2009/10/6/entrez PY - 2009/10/6/pubmed PY - 2010/1/15/medline SP - 105 EP - 11 JF - Behavioural brain research JO - Behav. Brain Res. VL - 207 IS - 1 N2 - RATIONALE: Systemic administration of cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is able to attenuate cardiovascular and behavioral (freezing) changes induced by re-exposure to a context that had been previously paired with footshocks. The brain sites mediating this effect, however, remain unknown. The medial prefrontal cortex (mPFC) has been related to contextual fear conditioning. OBJECTIVES: (1) To verify, using c-Fos immunocytochemistry, if the mPFC is involved in the attenuation of contextual fear induced by systemic administration of CBD; (2) to investigate if direct microinjections of CBD into mPFC regions would also attenuate contextual fear. RESULTS: Confirming previous results systemic administration of CBD (10mg/kg) decreased contextual fear and associated c-Fos expression in the prefrontal cortex (prelimbic and infralimbic regions). The drug also attenuated c-Fos expression in the bed nucleus of the stria terminalis (BNST). Direct CBD (30 nmol) microinjection into the PL prefrontal cortex reduced freezing induced by re-exposure to the aversively conditioned context. In the infralimbic (IL) prefrontal cortex, however, CBD (30 nmol) produced an opposite result, increasing the expression of contextual fear conditioning. This result was confirmed by an additional experiment where the conditioning session was performed under a less aversive protocol. CONCLUSION: These results suggest that the PL prefrontal cortex may be involved in the attenuation of contextual fear induced by systemic injection of CBD. They also support the proposition that the IL and PL play opposite roles in fear conditioning. A possible involvement of the BNST in CBD effects needs to be further investigated. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/19800921/Involvement_of_the_prelimbic_prefrontal_cortex_on_cannabidiol_induced_attenuation_of_contextual_conditioned_fear_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(09)00589-0 DB - PRIME DP - Unbound Medicine ER -