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Evidence for a role of GABAergic and glutamatergic signalling in the basolateral amygdala in endocannabinoid-mediated fear-conditioned analgesia in rats.
Pain. 2013 Apr; 154(4):576-85.PAIN

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 cannabinoid1 (CB1) receptors and interactions with GABAergic (GABAA 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 GABAA 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.

Authors+Show Affiliations

Pharmacology and Therapeutics, School of Medicine, University Road, National University of Ireland, Galway, Ireland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23414578

Citation

Rea, Kieran, et al. "Evidence for a Role of GABAergic and Glutamatergic Signalling in the Basolateral Amygdala in Endocannabinoid-mediated Fear-conditioned Analgesia in Rats." Pain, vol. 154, no. 4, 2013, pp. 576-85.
Rea K, Olango WM, Harhen B, et al. Evidence for a role of GABAergic and glutamatergic signalling in the basolateral amygdala in endocannabinoid-mediated fear-conditioned analgesia in rats. Pain. 2013;154(4):576-85.
Rea, K., Olango, W. M., Harhen, B., Kerr, D. M., Galligan, R., Fitzgerald, S., Moore, M., Roche, M., & Finn, D. P. (2013). Evidence for a role of GABAergic and glutamatergic signalling in the basolateral amygdala in endocannabinoid-mediated fear-conditioned analgesia in rats. Pain, 154(4), 576-85. https://doi.org/10.1016/j.pain.2012.12.021
Rea K, et al. Evidence for a Role of GABAergic and Glutamatergic Signalling in the Basolateral Amygdala in Endocannabinoid-mediated Fear-conditioned Analgesia in Rats. Pain. 2013;154(4):576-85. PubMed PMID: 23414578.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for a role of GABAergic and glutamatergic signalling in the basolateral amygdala in endocannabinoid-mediated fear-conditioned analgesia in rats. AU - Rea,Kieran, AU - Olango,Weredeselam M, AU - Harhen,Brendan, AU - Kerr,Daniel M, AU - Galligan,Rachel, AU - Fitzgerald,Sean, AU - Moore,Maeve, AU - Roche,Michelle, AU - Finn,David P, Y1 - 2012/12/31/ PY - 2012/03/14/received PY - 2012/08/25/revised PY - 2012/12/20/accepted PY - 2013/2/19/entrez PY - 2013/2/19/pubmed PY - 2013/9/21/medline SP - 576 EP - 85 JF - Pain JO - Pain VL - 154 IS - 4 N2 - 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 cannabinoid1 (CB1) receptors and interactions with GABAergic (GABAA 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 GABAA 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. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/23414578/Evidence_for_a_role_of_GABAergic_and_glutamatergic_signalling_in_the_basolateral_amygdala_in_endocannabinoid_mediated_fear_conditioned_analgesia_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3959(12)00682-3 DB - PRIME DP - Unbound Medicine ER -