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The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nocicpetive tone

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dc.contributor.author Olango, W.M.
dc.contributor.author Roche, Michelle
dc.contributor.author Ford, Gemma K.
dc.contributor.author Harhen, Brendan
dc.contributor.author Finn, David P.
dc.date.accessioned 2012-01-24T10:25:25Z
dc.date.available 2013-01-21T13:13:49Z
dc.date.issued 2011
dc.identifier.citation Olango WM, Roche M, Ford GK, Harhen B, Finn DP (2011). The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nocicpetive tone. British Journal of Pharmacology en_US
dc.identifier.uri http://hdl.handle.net/10379/2526
dc.description.abstract Background and purpose: Endocannabinoids in the midbrain periaqueductal grey (PAG) are involved in modulating 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 approach: Rats received intra-dlPAG administration of the CB1 receptor antagonist/inverse agonist rimonabant, or vehicle, prior to re-exposure to a context paired 24hrs previously with footshock. Formalin-evoked nociceptive behaviour and fear-related behaviours (freezing and 22kHz ultrasonic vocalisation) were assessed. In a separate cohort, alterations in 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 results: Re-exposure of rats to the context previously associated with footshock resulted in FCA. Intra-dlPAG administration of rimonabant significantly attenuated FCA and fear-related behaviours expressed in the presence of nociceptive tone. Conditioned fear in the absence of formalin-evoked nociceptive tone was associated with increased levels of the endocannabinoids (2-AG and AEA) and NAEs (PEA and OEA) in the dlPAG. FCA was specifically associated with an increase in AEA levels in the dlPAG. Conclusions and implications: These data suggest that conditioned fear to context mobilises endocannabinoids and NAEs in the dlPAG and support a role for the endocannabinoid system in the dlPAG in mediating the potent suppression of pain responding which occurs during exposure to conditioned aversive contexts. en_US
dc.format application/pdf en_US
dc.language.iso en en_US
dc.publisher Wiley en_US
dc.subject Pain en_US
dc.subject Fear en_US
dc.subject Cannabinoid type 1 (CB1) receptor en_US
dc.subject Endocannabinoids en_US
dc.subject N-acylethanolamines en_US
dc.subject Periaqueductal grey en_US
dc.subject Rats en_US
dc.subject Pharmacology & Therapeutics en_US
dc.title The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nocicpetive tone en_US
dc.type Article en_US
dc.local.publishedsource http://dx.doi.org/10.1111/j.1476-5381.2011.01478.x en_US
dc.description.peer-reviewed peer-reviewed en_US
dc.contributor.funder SFI en_US

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