title: Evidence for a role of GABAergic and glutamatergic signalling in the basolateral amygdala in endocannabinoid-mediated fear-conditioned analgesia in rats.
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: Pharmacology and Therapeutics, School of Medicine, University Road, National University of Ireland, Galway, Ireland NCBES Neuroscience Cluster and Centre for Pain Research, University Road, National University of Ireland, Galway, Ireland Physiology, School of Medicine, University Road, National University of Ireland, Galway, Ireland.
authors: Kieran
authors: K
authors: Rea
authors: Weredeselam M
authors: WM
authors: Olango
authors: Brendan
authors: B
authors: Harhen
authors: Daniel M
authors: DM
authors: Kerr
authors: Rachel
authors: R
authors: Galligan
authors: Sean
authors: S
authors: Fitzgerald
authors: Maeve
authors: M
authors: Moore
authors: Michelle
authors: M
authors: Roche
authors: David P
authors: DP
authors: Finn
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000698:Analgesia; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000378:metabolism* / Q000494:pharmacology; D004983:Ethanolamines / Q000378:metabolism; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D007839:Functional Laterality / Q000187:drug effects; D018682:GABA Agents / Q000494:pharmacology; D005989:Glycerides / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D010146:Pain / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology; D018079:Receptors, GABA / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D004983:Ethanolamines; D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D005989:Glycerides; C022203:N-acylethanolamines; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018079:Receptors, GABA; D017470:Receptors, Glutamate; C103505:AM 251; C094503:glyceryl 2-arachidonate