Study M353

Study name

Perrine SA 2014

Title

Ketamine reverses stress-induced depression-like behavior and increased GABA levels in the anterior cingulate: an 11.7 T 1H-MRS study in rats

Overall design

In this study male Sprague-Dawley rats were subjected to a modified chronic unpredictable stress (CUS) paradigm that used a random pattern of unpredictable stressors twice daily for 10 days to explore the early developmental stages of depression-like endophenotypes. Control rats were handled daily for 10 days. Some rats from each treatment group received an injection of ketamine (40 mg/kg) after the final stressor. One day following the final stressor rats were tested for behavioral effects in the forced swim test and then euthanized to collect trunk blood and anterior cingulate brain samples. GABA levels were measured in anterior cingulate samples ex vivo using proton magnetic resonance spectroscopy (1H-MRS) at 11.7 T. Rats were divided into the following 4 groups: (1) control group (handled daily and saline treatment), (2) CMS group (stressor plus saline treatment), (3) ketamine group (handled daily and ketamine treatment at the dose of 40 mg/kg), (4) CMS + ketamine group (stressor plus ketamine treatment at the dose of 40 mg/kg). The CMS stress procedure lasted for 10 days, and ketamine was injected intraperitoneally 3 h after the pre-swim (on day 10). Six samples in control group, 8 in CMS group, 5 in ketamine group, and 8 in CMS + ketamine group were used for MRS.

Study Type

Type1;

Type2;

Type3;

Data available

Unavailable

Organism

Rat; Sprague-Dawley rat;

Categories of depression

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

Healthy individuals; Healthy individuals; Healthy individuals;

Criteria for depression

Forced swimming test

Sample size

27

Tissue

Central; Brain; Anterior cingulate cortex;

Platform

NMR; NMR: Bruker 11.7 T magnet with Avance DRX-500 console (Bruker Biospin Corp., Billerica, MA);

PMID

24246571

DOI

10.1016/j.pnpbp.2013.11.003

Citation

Perrine SA, Ghoddoussi F, Michaels MS, et al. Ketamine reverses stress-induced depression-like behavior and increased GABA levels in the anterior cingulate: an 11.7 T 1H-MRS study in rats. Prog Neuropsychopharmacol Biol Psychiatry 2014;51:9-15.

Metabolite

Gamma-Aminobutyric acid;