Cannabinoid CB1 receptors in the medial prefrontal cortex modulate the expression of contextual fear conditioning

Autor(es)

Lisboa, Sabrina F. ^[1] ; Reis, Daniel G. ^[1] ; da Silva, Andreia Lopes ^[2] ; Correa, Fernando M. A. ^[1] ; Guimaraes, Francisco S. ^[1] ; Resstel, Leonardo B. M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14049900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, BR-14049900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY; v. 13, n. 9, p. 1163-1173, OCT 2010.
• Citações Web of Science: 46

Resumo

The ventral portion of the medial prefrontal cortex (vMPFC) has been related to the expression of contextual fear conditioning. This study investigated the possible involvement of CB(1) receptors in this aversive response. Male Wistar rats were submitted to a contextual aversive conditioning session and 48 h later re-exposed to the aversive context in which freezing and cardiovascular responses (increase of arterial pressure and heart rate) were recorded. The expression of CB(1) receptor-mRNA in the vMPFC was also measured using real time-PCR. In the first experiment intra-vMPFC administration of the CB(1) receptor agonist anandamide (AEA, 5 pmol/200 nl) or the AEA transport inhibitor AM404 (50 pmol/200 nl) prior to re-exposure to the aversive context attenuated the fear-conditioned responses. These effects were prevented by local pretreatment with the CB(1) receptor antagonist AM251 (100 pmol/200 nl). Using the same conditioning protocol in another animal group, we observed that CB(1) receptor mRNA expression increased in the vMPFC 48 h after the conditioning session. Although AM251 did not cause any effect by itself in the first experiment, this drug facilitated freezing and cardiovascular responses when the conditioning session employed a lesser aversive condition. These results indicated that facilitation of cannabinoid-mediated neurotransmission in the vMPFC by local CB(1) receptor activation attenuates the expression of contextual fear responses. Together they suggest that local endocannabinoid-mediated neurotransmission in the vMPFC can modulate these responses. (AU)

• Processo FAPESP: 07/03685-3 - Neurotransmissores típicos e atípicos em transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático