Inhibition of fatty acid amide hydrolase in the CNS prevents and reverses morphine tolerance in male and female mice.

ABSTRACT:

Background and purpose

Fatty acid amide hydrolase (FAAH) is an intracellular serine amidase that terminates the signalling of various lipid messengers involved in pain regulation, including anandamide and palmitoylethanolamide. Here, we investigated the effects of pharmacological or genetic FAAH removal on tolerance to the anti-nociceptive effects of morphine.

Experimental approach

We induced tolerance in male and female mice by administering twice-daily morphine for 7 days while monitoring nociceptive thresholds by the tail immersion test. The globally active FAAH inhibitor URB597 (1 and 3 mg·kg^-1 , i.p.) or the peripherally restricted FAAH inhibitor URB937 (3 mg·kg^-1 , i.p.) were administered daily 30 min prior to morphine, alone or in combination wit

SUBMITTER: Fotio Y 

PROVIDER: S-EPMC7280000 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature