Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression
Nico Liebenberg, Sâmia R L Joca, Gregers Wegener
Acta Neuropsychiatrica April 1, 2015 DOI: 10.1017/neu.2014.39 (opens in new tab)
Summary
AI-generated from the abstractPre-treatment with L-arginine, a nitric oxide precursor, blocked the antidepressant-like effect of ketamine in a genetic rat model of depression. Ketamine alone reduced immobility in the forced swim test and increased cGMP levels in the frontal cortex and hippocampus, but L-arginine prevented both effects. Ketamine also reduced constitutive nitric oxide synthase activity in the hippocampus, though this was not reversed by L-arginine. The results suggest the nitric oxide signaling pathway contributes to ketamine's antidepressant action.
Study at a glance
| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Flinders sensitive line (FSL) rats |
| Interventions | Ketamine L-arginine |
| Dose | 15 mg/kg ketamine, 500 mg/kg L-arginine |
| Key finding | L-arginine pre-treatment prevented the antidepressant-like effect of ketamine in the forced swim test and blocked ketamine-induced increases in cGMP levels in the frontal cortex and hippocampus. |
Abstract
ObjectiveWe investigated whether the nitric oxide (NO) precursor,l-arginine, can prevent the antidepressant-like action of the fast-acting antidepressant, ketamine, in a genetic rat model of depression, and/or induce changes in the glutamate (Glu)/N-methyl-d-aspartate receptor (NMDAR)/NO/cyclic guanosine monophosphate (cGMP) signalling pathway. Hereby it was evaluated whether the NO signalling system is involved in the antidepressant mechanism of ketamine.MethodsFlinders sensitive line (FSL) rats received single i.p. injections of ketamine (15 mg/kg) with/without pre-treatment (30 min prior) withl-arginine (500 mg/kg). Depression-like behaviour was assessed in the forced swim test (FST) in terms of immobility, and the activation state of the Glu/NMDAR/NO/cGMP pathway was evaluatedex vivoin the frontal cortex and hippocampus regions in terms of total constitutive NOS (cNOS) activity and cGMP concentration.Resultsl-Arginine pre-treatment prevented the antidepressant-like effect of ketamine in the FST, as well as a ketamine-induced increase in cGMP levels in the frontal cortex and hippocampus of FSL rats. Ketamine reduced cNOS activity only in the hippocampus, and this effect was not reversed byl-arginine.ConclusionBoth the behavioural and molecular results from this study indicate an involvement for the NO signalling pathway in the antidepressant action of ketamine. Although not easily interpretable, these findings broaden our knowledge of effects of ketamine on the NO system.