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

Abstract

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 CB1 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 CB1 receptor-mRNA in the vMPFC was also measured using real time-PCR. In the first experiment intra-vMPFC administration of the CB1 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 CB1 receptor antagonist AM251 (100 pmol/200 nl). Using the same conditioning protocol in another animal group, we observed that CB1 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 CB1 receptor activation attenuates the expression of contextual fear responses. Together they suggest that local endocannabinoid-mediated neurotransmission in the vMPFC can modulate these responses.

Modulation of Fear Memory by Dietary Polyunsaturated Fatty Acids via Cannabinoid Receptors

“…2008), and vmPFC (Lisboa et al, 2010) to the observed effects should be examined in a future study. In addition, because this memory is essential for individuals' survival, it seems that a warning is necessary in excessive reduction of this memory.…”

“…On the other hand, systemic administration of the CB 1 agonists WIN55,212-2 (WIN) or HU-210 impairs contextual fear conditioning in rats (Mackowiak et al, 2009;. In addition, pre-test microinjection of another CB 1 agonist, anandamide, into the dorsolateral periaqueductal gray (PAG) or ventromedial prefrontal cortex (vmPFC) impairs contextual fear conditioning in rats (Lisboa et al, 2010;Resstel et al, 2008). These results consistently suggest that activation of CB 1 receptors reduces contextual fear memory.…”

Medial prefrontal cortex endocannabinoid system modulates baroreflex activity through CB1receptors

“…In addition, results from our group showed that expression of mRNA for CB 1 receptors in the vMPFC is increased in animals exposed to a protocol of contextual fear conditioning. Moreover, when these animals were treated with the CB 1 receptor antagonist AM251 in the vMPFC, they exhibit an increase of both cardiovascular and behavior responses associated with reexposure to the aversive context (30). Finally, the local administration of an antagonist of NMDA receptors in the vMPFC evokes a decrease of both cardiovascular and behavior responses associated with contextual fear conditioning (47).…”

“…All groups of animals used in our study received three sets of phenylephrine or SNP infusion to determine control values of baroreflex activity. In the sequence, the first group received a microinjection of 200 nl of 10% DMSO dissolved in saline (0.9% NaCl); the second group received a microinjection of 200 nl of AM251 [10, 100, or 300 pmol (30)]; the third group received a microinjection of 200 nl of AM404 [50 or 100 pmol (30)]; the fourth group received a microinjection of 200 nl of URB597 [100 pmol (31)]; the fifth group received bilateral microinjections of 200 nl of AM251 (10 pmol) and 5 min later AM404 (100 pmol) or URB597 (100 pmol). In all experimental groups, phenylephrine and SNP infusions were repeated 10 and 60 min after the microinjection of drugs.…”

Os receptores TRPV₁ do córtex pré-frontal medial ventral modulam a atividade do barorreflexo cardíaco em ratos

“…O CPFMv está envolvido com a modulação de respostas emocionais e autonômicas em situações aversivas (Lisboa et al, 2010b Como os sistemas endovanilóide e endocanabinóide presentes no CPFMv interagem entre si (Fogaca et al, 2012), o bloqueio de receptores CB1 do CPFMv, poderia deslocar a anandamida para a ativação de receptores TRPV1, o que pode ser responsável pelo aumento do comportamento do tipo ansiogênico e das alterações cardiovasculares associados ao contexto aversivo (Lisboa et al, 2010a). Deste modo, os receptores TRPV1 presentes no CPFMv também podem participar da modulação barorreflexa durante reações de defesa, podendo estar envolvidos, por exemplo, nos ajustes que facilitam a taquicardia reflexa observada em ratos submetidos ao modelo do estresse por restrição (Crestani et al, 2010), permitindo também o aumento de PA concomitante ao aumento de FC, característico da resposta autonômica que acontece durante situações aversivas (Resstel et al, 2008).…”