Aspirin-triggered lipoxin induces CB1-dependent catalepsy in mice

• Published in: Neuroscience letters Vol. 470; no. 1; pp. 33 - 37
• Main Authors: PAMPLONA, Fabrício A, MENEZES-DE-LIMA, Octávio, TAKAHASHI, Reinaldo N
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier 05.02.2010
• Subjects: Animals; Arachidonate 5-Lipoxygenase - metabolism; Arachidonic Acids - metabolism; Aspirin - pharmacology; Biological and medical sciences; Catalepsy - chemically induced; Catalepsy - metabolism; Central Nervous System Agents - pharmacology; Cyclooxygenase Inhibitors - pharmacology; Endocannabinoids; Fundamental and applied biological sciences. Psychology; Lipoxins - metabolism; Male; Mice; Models, Neurological; Piperidines - pharmacology; Polyunsaturated Alkamides - metabolism; Pyrazoles - pharmacology; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - metabolism; Receptors, Lipoxin - antagonists & inhibitors; Receptors, Lipoxin - metabolism; Vertebrates: nervous system and sense organs; Enzyme; Rodentia; Aspirin-triggered lipoxin; Acetylsalicylic acid; Cannabinoid; Anandamide; Vertebrata; Mammalia; Endocannabinoid; Mouse; 15-Epi-lipoxin A; Animal; Oxidoreductases; Lipoxygenase
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2009.12.050

Evidence are that inhibition of cyclooxygenase 2 (COX-2) enhances endocannabinoid signaling, indicating a crosstalk between these two eicosanoid pathways. Aspirin, a non-selective COX inhibitor, acetylates COX-2 with generation of a lipoxygenase (LOX) substrate, whose end product is the 15-epi-lipoxin A(4) (15-epi-LXA(4)), an aspirin-triggered lipoxin. Our objective was to investigate whether 15-epi-LXA(4) would potentiate in vivo effects of the endocannabinoid anandamide (AEA). Catalepsy was selected as a behavioral parameter and tested 5 min after AEA injection in all experiments. AEA induced dose-dependent (200 pmol/2 microl, i.c.v.) catalepsy. A sub-dose of AEA (10 pmol/2 microl, i.c.v.) was potentiated by aspirin (300 mg/kg, p.o.) via a 5-LOX-dependent step. The cataleptic effect induced by the interaction between sub-doses of 15-epi-LXA(4) (0.01 pmol/2 microl, i.c.v.) and AEA (10 pmol/2 microl, i.c.v.) was prevented by the cannabinoid CB(1) receptors antagonist SR141716A (1mg/kg, i.p.), but not by the antagonist of lipoxin ALX receptors Boc-2 (10 microg/kg, i.p.). While previous studies have shown that COX inhibition itself may enhance endocannabinoid effects, here we add another piece of evidence revealing that a LOX-derivative produced in consequence of COX-2 acetylation participates in this process.