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Study M177

Study name

Chowdhury GM 2017

Title

Transiently increased glutamate cycling in rat PFC is associated with rapid onset of antidepressant-like effects

Overall design

The aim of this study was to demonstrate that the antidepressant-like efficacy of three unique drugs, with reported rapid onset antidepressant properties, is coupled with a rapid transient rise in glutamate cycling in the medial prefronal cortex (mPFC) of awake rats as measured by ex vivo 1H-[13C]-nuclear magnetic resonance spectroscopy. Rats were acutely pretreated by intraperitoneal injection with a single dose of ketamine (1, 3, 10, 30 and 80 mg/kg), Ro 25-6981 (1, 3 and 10 mg/kg), scopolamine (5, 25 and 100 ug/kg) or vehicle (controls) (n = 6-8 per group). At fixed times after drug injection, animals received an intravenous infusion of [1,6-13C2]glucose for 8 min to enrich the amino-acid pools of the brain with 13C, followed by rapid euthanasia. The mPFC was dissected, extracted with ethanol and metabolite 13C enrichments were measured.

Study Type

Type3;

Data available

Unavailable

Organism

Rat; Sprague-Dawley rat;

Categories of depression

Healthy individuals; Healthy individuals; Healthy individuals;

Criteria for depression

Forced swimming test

Sample size

N/A

Tissue

Central; Brain; Medial prefrontal cortex;

Peripheral; Blood; Plasma;

Platform

NMR; NMR: Bruker AVANCE spectrometer (Bruker Instruments, Billerica, MA);

PMID

27067013

DOI

10.1038/mp.2016.34

Citation

Chowdhury GM, Zhang J, Thomas M, et al. Transiently increased glutamate cycling in rat PFC is associated with rapid onset of antidepressant-like effects. Mol Psychiatry 2017;22(1):120-126.

Metabolite

Gamma-Aminobutyric acid;

L-Glutamic acid;

L-Glutamine;