Evidence for a role of GABAergic and glutamatergic signalling in the basolateral amygdala in endocannabinoid-mediated fear-conditioned analgesia in rats
Rea, Kieran Olango, Weredeselam M. Harhen, Brendan Kerr, Daniel M. Galligan, Rachel Fitzgerald, Sean Moore, Maeve Roche, Michelle Finn, David P.
Rea, Kieran
Olango, Weredeselam M.
Harhen, Brendan
Kerr, Daniel M.
Galligan, Rachel
Fitzgerald, Sean
Moore, Maeve
Roche, Michelle
Finn, David P.
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Publication Date
2012-12-31
Keywords
AM251, Amygdala, Bicuculline, Cannabinoid(1) (CB1) receptor, MPEP, Pain, STRESS-INDUCED ANALGESIA, FATTY-ACID AMIDE, CANNABINOID RECEPTOR CB1, VANILLOID TYPE-1 RECEPTORS, LONG-TERM POTENTIATION, CENTRAL-NERVOUS-SYSTEM, PERIAQUEDUCTAL GRAY, HEMISPHERIC LATERALIZATION, INFLAMMATORY PAIN, FOS EXPRESSION
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Article
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Rea K, Olango WM, Harhen B, Kerr DM, Galligan R, Fitzgerald S, Moore M,Roche M, Finn, DP (2013). Evidence for a role ofGABAergic and glutamatergic signalingin thebasolateral amygdala in endocannabinoid-mediated fear-conditioned analgesiainRats. Pain, 154(4),576 85. DOI: https://doi.org/10.1016/j.pain.2012.12.021
Abstract
The basolateral amygdala (BLA) is a key substrate facilitating the expression of fear-conditioned analgesia (FCA). However, the neurochemical mechanisms in the BLA which mediate this potent suppression of pain responding during fear remain unknown. The present study investigated the role of cannabinoid(1) (CB1) receptors and interactions with GABAergic (GABA(A) receptor) and glutamatergic (metabotropic glutamate receptor type 5; mGluR5) signalling in the BLA in formalin-evoked nociceptive behaviour and FCA in rats. Reexposure to a context previously paired with foot shock significantly reduced formalin-evoked nociceptive behaviour. Systemic or intra-BLA microinjection of the CB1 receptor antagonist/inverse agonist AM251 prevented this expression of FCA, while injection of AM251 into the central nucleus of the amygdala did not. The suppression of FCA by systemic AM251 administration was partially attenuated by intra-BLA administration of either the GABA(A) receptor antagonist bicuculline or the mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine, (MPEP). Bilateral microinjection of MPEP, but not bicuculline, alone into the BLA enhanced formalin-evoked nociceptive behaviour. Postmortem analyses revealed that FCA was associated with a significant increase in tissue levels of anandamide in the BLA side contralateral to intraplantar formalin injection. In addition, fear-conditioned rats exhibited a robust formalin-induced increase in levels of 2-arachidonyl glycerol and N-palmitoylethanolamide in the ipsilateral and contralateral BLA, respectively. These data suggest that CB1 receptors in the BLA facilitate the expression of FCA, through a mechanism which is likely to involve the modulation of GABAergic and glutamatergic signalling. (c) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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Elsevier
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Attribution-NonCommercial-NoDerivs 3.0 Ireland