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Pharmacological blockade of PPARα exacerbates inflammatory pain-related impairment of spatial memory in rats

Gaspar, Jessica C.
; 
Healy, Catherine
; 
Ferdousi, Mehnaz I.
; 
Roche, Michelle
; 
Finn, David P.
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Identifiers
http://hdl.handle.net/10379/16843
 https://doi.org/10.13025/22573
Publication Date
2021-05-27
Keywords
peroxisome-proliferator activated receptor, cognition, anxiety, spatial memory, complete Freund adjuvant, PEA, OEA, dorsal hippocampus
Type
Article
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Citation
Gaspar, Jessica C., Healy, Catherine, Ferdousi, Mehnaz I., Roche, Michelle, & Finn, David P. (2021). Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats. Biomedicines, 9(6), 610. doi:10.3390/biomedicines9060610
Abstract
Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that exist in three isoforms: PPAR¿, PPARß/¿ and PPAR¿. Studies suggest that the PPAR signalling system may modulate pain, anxiety and cognition. The aim of the present study was to investigate whether endogenous signalling via PPARs differentially modulates innate anxiety responses and mnemonic function in the presence and absence of inflammatory pain. We examined the effects of intraperitoneal administration of GW6471 (PPAR¿ antagonist), GSK0660 (PPARß/¿ antagonist), GW9662 (PPAR¿ antagonist), and N-palmitoylethanolamide (PEA) on rat behaviour in the elevated plus maze (EPM), open field (OF), light-dark box (LDB), and novel object recognition (NOR) tests in the presence or absence of chronic inflammatory pain. Complete Freund's Adjuvant (CFA)-injected rats exhibited impaired recognition and spatial mnemonic performance in the NOR test and pharmacological blockade of PPAR¿ further impaired spatial memory in CFA-treated rats. N-oleoylethanolamide (OEA) levels were higher in the dorsal hippocampus in CFA-injected animals compared to their counterparts. The results suggest a modulatory effect of CFA-induced chronic inflammatory pain on cognitive processing, but not on innate anxiety-related responses. Increased OEA-PPAR¿ signalling may act as a compensatory mechanism to preserve spatial memory function following CFA injection.
Funder
Conselho Nacional de Pesquisa (CNPq) Brazil
Publisher
MDPI
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
cbn
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Physiology (Scholarly Articles)