Attenuation of fear‐conditioned analgesia in rats by monoacylglycerol lipase inhibition in the anterior cingulate cortex: Potential role for CB 2 receptors

Autor:	Michelle Roche, Darragh Mattimoe, David P. Finn, Louise Corcoran
Přispěvatelé:	Science Foundation Ireland
Rok vydání:	2020
Předmět:	0301 basic medicine Pharmacology AM251 Cannabinoid receptor CB2 receptors Chemistry monoacylglycerol lipase inhibition Antagonist fear‐conditioned analgesia Endocannabinoid system rats Monoacylglycerol lipase anterior cingulate cortex 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Cannabinoid receptor type 2 medicine Receptor psychological phenomena and processes 030217 neurology & neurosurgery Anterior cingulate cortex medicine.drug
Zdroj:	British Journal of Pharmacology. 177:2240-2255
ISSN:	1476-5381 0007-1188
Popis:	Improved understanding of brain mechanisms regulating endogenous analgesia is important from a fundamental physiological perspective and for identification of novel therapeutic strategies for pain. The endocannabinoid system plays a key role in stress-induced analgesia, including fear-conditioned analgesia (FCA), a potent form of endogenous analgesia. Here we studied the role of the endocannabinoid 2-arachidonoyl glycerol (2-AG) within the anterior cingulate cortex (ACC; a brain region implicated in the affective component of pain) in FCA in rats. FCA was modelled in male Lister-hooded rats by assessing formalin-evoked nociceptive behaviour in an arena previously paired with footshock. The effects of intra-ACC administration of MJN110 (inhibitor of monoacylglycerol lipase [MGL], the primary enzyme catabolising 2-AG), AM630 (CB2 receptor antagonist), AM251 (CB1 receptor antagonist), or MJN110+AM630 on FCA were assessed. MJN110 attenuated FCA when microinjected into the ACC, an effect associated with increased levels of 2-AG in the ACC. This effect of MJN110 on FCA was unaltered by co-administration of AM251 but was blocked by AM630, which alone reduced nociceptive behaviour in non-fear-conditioned rats. RT-qPCR confirmed that mRNA encoding CB1 and CB2 receptors was detectable in the ACC of formalin-injected rats, and unchanged in those expressing FCA. These results suggest that a MGL substrate in the ACC, likely 2-AG, modulates FCA, and that within the ACC, 2-AG-CB2 receptor signalling may suppress this form of endogenous analgesia. These results may facilitate increased understanding and improved treatment of, pain- and fear-related disorders and their comorbidity. This work was funded by grants from the Science Foundation Ireland (10/IN.1/B2976) and the Irish Research Council. peer-reviewed 2021-01-22
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b66af05624919c13b180af855766a12 https://doi.org/10.1111/bph.14976 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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