Publication

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

Olango, W.M.
Roche, Michelle
Ford, Gemma K.
Harhen, Brendan
Finn, David P.
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
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.
Funder
Publisher
Wiley
Publisher DOI
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland