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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 nociceptive tone.
Br J Pharmacol. 2012 Apr; 165(8):2549-60.BJ

Abstract

BACKGROUND AND PURPOSE

Endocannabinoids 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 APPROACH

Rats received intra-dlPAG administration of the CB(1) 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 RESULTS

Re-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 IMPLICATIONS

Conditioned 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.

LINKED ARTICLES

This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.

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Authors+Show Affiliations

Olango WM
Pharmacology and Therapeutics Physiology, School of Medicine NCBES Neuroscience Cluster Centre for Pain Research, National University of Ireland, Galway, Ireland.
Roche M
No affiliation info available
Ford GK
No affiliation info available
Harhen B
No affiliation info available
Finn DP
No affiliation info available

MeSH

AnalgesiaAnimalsCannabinoid Receptor ModulatorsConditioning, PsychologicalEndocannabinoidsFearFormaldehydeMaleMotor ActivityPainPeriaqueductal GrayPiperidinesPyrazolesRatsReceptor, Cannabinoid, CB1RimonabantUltrasonics

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21564082

Citation

Olango, W M., et al. "The Endocannabinoid System in the Rat Dorsolateral Periaqueductal Grey Mediates Fear-conditioned Analgesia and Controls Fear Expression in the Presence of Nociceptive Tone." British Journal of Pharmacology, vol. 165, no. 8, 2012, pp. 2549-60.
Olango WM, Roche M, Ford GK, et al. The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nociceptive tone. Br J Pharmacol. 2012;165(8):2549-60.
Olango, W. M., Roche, M., Ford, G. K., Harhen, B., & Finn, D. P. (2012). The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nociceptive tone. British Journal of Pharmacology, 165(8), 2549-60. https://doi.org/10.1111/j.1476-5381.2011.01478.x
Olango WM, et al. The Endocannabinoid System in the Rat Dorsolateral Periaqueductal Grey Mediates Fear-conditioned Analgesia and Controls Fear Expression in the Presence of Nociceptive Tone. Br J Pharmacol. 2012;165(8):2549-60. PubMed PMID: 21564082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nociceptive tone. AU - Olango,W M, AU - Roche,M, AU - Ford,G K, AU - Harhen,B, AU - Finn,D P, PY - 2011/5/14/entrez PY - 2011/5/14/pubmed PY - 2012/7/28/medline SP - 2549 EP - 60 JF - British journal of pharmacology JO - Br J Pharmacol VL - 165 IS - 8 N2 - BACKGROUND AND PURPOSE: Endocannabinoids 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 APPROACH: Rats received intra-dlPAG administration of the CB(1) 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 RESULTS: Re-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 IMPLICATIONS: Conditioned 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. LINKED ARTICLES: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/21564082/The_endocannabinoid_system_in_the_rat_dorsolateral_periaqueductal_grey_mediates_fear_conditioned_analgesia_and_controls_fear_expression_in_the_presence_of_nociceptive_tone_ L2 - https://doi.org/10.1111/j.1476-5381.2011.01478.x DB - PRIME DP - Unbound Medicine ER -