Influx of kynurenine into the brain is involved in the reduction of ethanol consumption induced by Ro 61-8048 after chronic intermittent ethanol in mice.

ABSTRACT:

Background and purpose

The kynurenine pathway has been proposed as a target for modulating drug abuse. We previously demonstrated that inhibition of kynurenine 3-monooxygenase (KMO), using Ro 61-8048, reduces ethanol consumption in a binge drinking model. Here, we investigate the effect of the kynurenine pathway modulation in ethanol-dependent mice.

Experimental approach

Adult male and female mice were subjected to a Chronic Intermittent Ethanol (CIE) paradigm. On the last day of CIE, mice were treated with Ro 61-8048, Ro 61-8048 + PNU-120596, a positive allosteric modulator of α7nAChR, and Ro 61-8048 + L-leucine or probenecid, which blocks the influx or efflux of kynurenine from the brain, respectively. Ethanol, water consumption and preference were measured and kynurenine

SUBMITTER: Gil de Biedma-Elduayen L 

PROVIDER: S-EPMC9314579 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature