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Olango, WM,Roche, M,Ford, GK,Harhen, B,Finn, DP
2012
April
British Journal Of Pharmacology
The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nociceptive tone
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pain fear cannabinoid type 1 (CB1) receptor endocannabinoids N-acylethanolamines periaqueductal grey rats STRESS-INDUCED ANALGESIA ROSTRAL VENTROMEDIAL MEDULLA ACID AMIDE HYDROLASE ENDOGENOUS CANNABINOID SYSTEM FOS-LIKE IMMUNOREACTIVITY DEFENSIVE BEHAVIOR CB1 RECEPTORS ELECTRICAL-STIMULATION BASOLATERAL AMYGDALA SPINAL NOCICEPTION
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BACKGROUND AND PURPOSEEndocannabinoids in the midbrain periaqueductal grey (PAG) modulate nociception and unconditioned stress-induced analgesia; however, their role in fear-conditioned analgesia (FCA) has not been examined. The present study examined the role of the endocannabinoid system in the dorsolateral (dl) PAG in formalin-evoked nociceptive behaviour, conditioned fear and FCA in rats.EXPERIMENTAL APPROACHRats received intra-dlPAG administration of the CB1 receptor antagonist/inverse agonist rimonabant, or vehicle, before re-exposure to a context paired 24 h previously with foot shock. Formalin-evoked nociceptive behaviour and fear-related behaviours (freezing and 22 kHz ultrasonic vocalization) were assessed. In a separate cohort, levels of endocannabinoids [2-arachidonoyl glycerol (2-AG) and N-arachidonoyl ethanolamide (anandamide; AEA)] and the related N-acylethanolamines (NAEs) [N-palmitoyl ethanolamide (PEA) and N-oleoyl ethanolamide (OEA)] were measured in dlPAG tissue following re-exposure to conditioned context in the presence or absence of formalin-evoked nociceptive tone.KEY RESULTSRe-exposure of rats to the context previously associated with foot shock resulted in FCA. Intra-dlPAG administration of rimonabant significantly attenuated FCA and fear-related behaviours expressed in the presence of nociceptive tone. Conditioned fear without formalin-evoked nociceptive tone was associated with increased levels of 2-AG, AEA, PEA and OEA in the dlPAG. FCA was specifically associated with an increase in AEA levels in the dlPAG.CONCLUSIONS AND IMPLICATIONSConditioned fear to context mobilises endocannabinoids and NAEs in the dlPAG. These data support a role for endocannabinoids in the dlPAG in mediating the potent suppression of pain responding which occurs during exposure to conditioned aversive contexts.
DOI 10.1111/j.1476-5381.2011.01478.x
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