AMPA glutamate receptors mediate the antidepressant-like effects of N-acetylcysteine in the mouse tail suspension test

Abstract

The aim of this study was to investigate the involvement of noradrenaline, serotonin, and subtypes of glutamate receptors in the antidepressant-like effects of N-acetylcysteine (NAC). The tail suspension test was used with male CF1 albino mice. D,L-α-methyl-ρ-tyrosine and ρ-chlorophenylalanine methyl ester hydrochloride were used as synthesis inhibitors of noradrenaline and serotonin, respectively. N-methyl-D-aspartate (NMDA) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione were used as an NMDA receptor agonist and an α-amino acid-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA) receptor antagonist, respectively. NAC (10, 25, and 50 mg/kg intraperitoneally) significantly (P<0.05) decreased tail suspension test immobility time, whereas pretreatment with D,L-α-methyl-ρ-tyrosine, ρ-chlorophenylalanine methyl ester hydrochloride, and NMDA partially prevented (P<0.05) the effects of NAC (25 mg/kg), and pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione completely abolished (P<0.01) this effect. The study corroborates the antidepressant-like effects of NAC in the TST, a model with a well-established predictive value. The results point to the key role of AMPA receptors in the mechanism of the antidepressant-like action of NAC. Like other AMPA potentiators, NAC indirectly modulates noradrenaline and serotonin pathways. It is suggested that the value of NAC as an antidepressant arises from combined and intertwined effects on a variety of pathways.

Involvement of the catecholaminergic system on the antidepressant-like effects ofAlpinia zerumbetin mice

“…Specifically, the modulation of AMPA receptors is associated with the antidepressant effects of compounds such as lithium, ketamine, and N-acetylcysteine (Gould et al, 2008;Linck et al, 2012;Zhou et al, 2013). Our results show that the blockade of AMPA receptors did not modify the effect of HEA in the TST; however, we cannot exclude the participation of NMDA or metabotropic glutamate receptors.…”

“…in a constant volume of 0.1 mL/10 g body weight. The administration schedule and the doses of AMPT, PCPA, and NBQX were selected from the literature (Linck et al, 2012;Rodrigues et al, 2002;Rojas-Corrales et al, 2005) and tested in pilot experiments in our laboratory; all the selected doses did not modify locomotion in the open field or the immobility time in the TSTs (data not shown).…”

Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids

“…Corroborating this hypothesis, antioxidant administration prevented the decreased sweet food intake, increased immobility time, and increased adrenal gland weight. Though specific trials for antidepressant effects in depression are still lacking, NAC shows antidepressant-like activity in several preclinical models; studies corroborate the antidepressant-like effects of NAC in rats subjected to the forced swimming test (Ferreira et al 2008) and in mice subjected to the tail suspension test (Linck et al 2012). Additionally, the chronic administration of NAC resulted in a dose-dependent reduction in immobility time in bulbectomized rats and resulted in a significant increase in cellular antioxidant mechanisms (superoxide dismutase activity) in the frontal cortex, hippocampus, and striatum (Smaga et al 2012).…”

Effects of N-acetylcysteine and imipramine in a model of acute rhythm disruption in BALB/c mice

“…*p50.05 compared to all other groups at same cycle, ANOVA/SNK. is highlighted by the key role of AMPA receptors in the antidepressant-like effects of NAC (Linck et al, 2012).…”

“…Following the interest raised by reports of the unique antidepressant pattern of sub-anesthetic doses of ketamine, much research has focused on glutamate modulators. Nacetylcysteine (NAC), a glutamate modulator devoid of the adverse effects common to most NMDA antagonists, have been reported to possess antidepressant-like effects in mice (Costa-Campos et al, 2013;Ferreira et al, 2008;Linck et al, 2012;Smaga et al, 2012) and in the depressive phase of bipolar patients (Berk et al, 2008).…”