Study M496

Study name

Bortolato M 2007

Title

Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597 in a rat model of chronic mild stress

Overall design

The aim of this study was to investigate the impact of chronic treatment with the selective fatty acid amide hydrolase (FAAH) inhibitor, URB597 (also termed KDS-4103), on the outcomes of the chronic mild stress (CMS) in rats, a behavioral model with high isomorphism to human depression. Rats were divided into the following 10 groups (n = 12 in each group): (1) control group (vehicle treatment), (2) CMS group (stressor plus vehicle treatment), (3) CMS + imipramine group (stressor plus imipramine treatment at the dose of 20 mg/kg I.P.), (4) CMS + low dose of URB597 group (stressor plus URB597 treatment at the dose of 0.03 g/kg I.P.), (5) CMS + middle dose of URB597 group (stressor plus URB597 treatment at the dose of 0.1 g/kg I.P.), (6) CMS + high dose of URB597 group (stressor plus URB597 treatment at the dose of 0.3 g/kg I.P.), (7) imipramine group (imipramine treatment at the dose of 20 mg/kg I.P.), (8) low dose of URB597 group (URB597 treatment at the dose of 0.03 g/kg I.P.), (9) middle dose of URB597 group (URB597 treatment at the dose of 0.1 g/kg I.P.), and (10) high dose of URB597 group (URB597 treatment at the dose of 0.3 g/kg I.P.). The CMS stress procedure lasted for 10 weeks, and drugs were administered once per day during the last 5 weeks of model building period. Endocannabinoids and related lipids of select brain regions were extracted with methanol-chloroform, fractionated by open-bed silica gel chromatography, and quantified by isotopedilution liquid chromatography/mass spectrometry (LC/MS).

Study Type

Type1;

Type2;

Data available

Unavailable

Organism

Rat; Wistar rat;

Categories of depression

Animal model; Chronic mild stress model; Chronic mild stress model;

Criteria for depression

Sucrose preference test

Sample size

72

Tissue

Central; Brain; Midbrain;

Central; Brain; Thalamus;

Central; Brain; Prefrontal cortex;

Central; Brain; Hippocampus;

Central; Brain; Striatum;

Platform

MS-based; LC-MS: not reported;

PMID

17511970

DOI

10.1016/j.biopsych.2006.12.001

Citation

Bortolato M, Mangieri RA, Fu J, et al. Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597 in a rat model of chronic mild stress. Biol Psychiatry. 2007;62(10):1103-10.

Metabolite

MG(0:0/20:4(5Z,8Z,11Z,14Z)/0:0);

Anandamide;