The prefrontal cortical endocannabinoid system modulates fear–pain interactions in a subregion‐specific manner

Abstract

These results suggest important and differing roles for FAAH substrates or CB receptors in the PrL, IfL and ACC in the expression of FCA and conditioned fear in the presence of nociceptive tone.

Attenuation of fear‐conditioned analgesia in rats by monoacylglycerol lipase inhibition in the anterior cingulate cortex: Potential role for CB2 receptors

“…Monoacylglycerol lipase inhibition in the anterior cingulate cortex attenuated the expression of fear‐conditioned analgesia, while having no effect on the expression of contextually induced freezing, locomotor activity (distance moved) or defecation. These findings together indicate that the expression of fear‐conditioned analgesia specifically, and not locomotor activity, fear‐related freezing or defecation, is suppressed by an monoacylglycerol lipase substrate in the anterior cingulate cortex and extend our previous work demonstrating that the medial prefrontal cortex is an important neural substrate for fatty acid amide hydrolase substrate‐ and/or CB 1 receptor‐mediated regulation of fear‐conditioned analgesia (Rea et al, ), alongside the ventral hippocampus (Ford et al, ), dorsolateral periaqueductal grey (Olango et al, ) and the basolateral amygdala (Rea et al, ; Roche et al, ). Moreover, these data are the first to suggest that the anterior cingulate cortex is an important neural substrate for fear‐conditioned analgesia and its modulation by the endocannabinoid system.…”

“…The design and time course of the experiments was identical to that depicted in fig. 1 of Rea et al (), with the exception of the drugs administered. The experimental procedures conformed to the BJP guidelines (Curtis et al, 2018).…”

“…The anterior cingulate cortex is involved in the modulation of fear behaviour (Cullen, Gilman, Winiecki, Riccio, & Jasnow, ; Einarsson, Pors, & Nader, ; Falconi‐Sobrinho, Anjos‐Garcia, de Oliveira, & Coimbra, ), the cognitive‐affective component of pain (Johansen, Fields, & Manning, ) and in the top‐down descending modulation of pain (Calejesan et al, ; Fuchs, Peng, Boyette‐Davis, & Uhelski, ). Recently, we have reported a role for the CB 1 receptor (antinociceptive) and fatty acid amide hydrolase substrates (antinociceptive or pronociceptive) in the infralimbic and prelimbic, but not in the anterior cingulate cortex, in fear‐conditioned analgesia (Rea, McGowan, Corcoran, Roche, & Finn, ). However, the role of monoacylglycerol lipase/2‐AG and CB 2 receptors in the anterior cingulate cortex in expression of fear‐conditioned analgesia has not yet been investigated and is the focus of this current study.…”

Pharmacological Blockade of PPAR Isoforms Increases Conditioned Fear Responding in the Presence of Nociceptive Tone

“…The FCA paradigm was essentially as described in our previous studies [56,62,63]. Briefly, there were two phases: conditioning (day 1) and test (day 2).…”

Cannabinoids and their actions: An update

“…The rest of the research papers look at cannabinoids in animal models with diverse elements of a CNS focus. Thus, one paper focusses on prefrontal cortex regulation of pain (Rea, McGowan, Corcoran, Roche, & Finn, 2019), while another looks at species differences in cannabinoid-induced convulsions (Whalley et al, 2019), and a third investigates endocannabinoid regulation of feeding (Sticht et al, 2019). Two papers look at features of reward and dependency: One looks at the roles of CB 1 and CB 2 receptors on behavioural responses to cocaine (Gobira et al, 2019).…”