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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.

Links

Publisher Full Text

Grapherence [↓23]

Authors+Show Affiliations

Lemos JI

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

Resstel LB

Guimarães FS

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 -