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Pain ; 154(4): 576-585, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23414578

RESUMEN

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.


Asunto(s)
Amígdala del Cerebelo/fisiología , Analgesia , Condicionamiento Psicológico/fisiología , Endocannabinoides/metabolismo , Miedo/fisiología , Receptores de GABA/fisiología , Receptores de Glutamato/fisiología , Transducción de Señal/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Ácidos Araquidónicos/farmacología , Agonistas de Receptores de Cannabinoides/farmacología , Condicionamiento Psicológico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Endocannabinoides/farmacología , Etanolaminas/metabolismo , Fármacos actuantes sobre Aminoácidos Excitadores/farmacología , Miedo/efectos de los fármacos , Lateralidad Funcional/efectos de los fármacos , GABAérgicos/farmacología , Glicéridos/farmacología , Inyecciones Intraventriculares , Masculino , Dolor/psicología , Dimensión del Dolor/efectos de los fármacos , Piperidinas/farmacología , Pirazoles/farmacología , Ratas , Receptor Cannabinoide CB1/fisiología , Transducción de Señal/efectos de los fármacos
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