Acute stress‐mediated increases in extracellular glutamate levels in the rat amygdala: differential effects of antidepressant treatment

Abstract

Depressive illness is associated with changes in amygdalar volume, and stressful life events are known to precipitate depressive episodes in this patient population. Stress affects amygdalar synaptic plasticity and several neurotransmitter systems have been implicated in stress-mediated changes in the brain, including the glutamatergic system. However, the role of the glutamatergic system in stress-mediated plasticity in the amygdala remains to be determined. Accordingly the current study examined the stress modulation of extracellular glutamate levels in the basolateral nucleus (BLA) and the central nucleus (CeA) of the amygdala by in vivo microdialysis. Acute stress increased extracellular glutamate levels in the BLA and CeA, although the dynamics of these stress-mediated changes were dramatically different in these amygdalar nuclei. Tetrodotoxin administration reduced basal, and completely eliminated stress-mediated increases in glutamate efflux in the amygdala, demonstrating that stress effects are dependent on local axonal depolarization. Moreover, stress-mediated increases in glutamate efflux in the BLA were inhibited by the antidepressant tianeptine but not by the selective serotonin-reuptake inhibitor fluoxetine. Collectively, these data demonstrate that stress-induced modulation of glutamate neurochemistry reflects a fundamental pathological change that may contribute to the aetiology and progression of depressive illness, and suggest that some antidepressants such as tianeptine may elicit their clinical effects by modulation of glutamatergic neurotransmission.

Self-Regulation of Breathing as a Primary Treatment for Anxiety

“…In addition, membrane depolarization is essential for contraction of skeletal muscle (Liu et al 2009), suggesting that increased muscle tension during stress may be the result of widespread depolarization. During stress, the release of the excitatory neurotransmitter glutamate in the amygdala (Reznikov et al 2007), and prefrontal cortex is mediated by depolarization (Musazzi et al 2010). Stress and depression are also associated with increased amygdala activity and chronic stress leads to neuronal hyperactivity in the amygdala, suggesting that a reduction in this excitatory drive may be a potential treatment (Padival et al 2013).…”

The Same Antidepressant Elicits Contrasting Patterns of Synaptic Changes in the Amygdala vs Hippocampus

“…Tianeptine-induced decrease in NMDA-EPSCs reported here suggests a similar mechanism in the amygdala. Further, Reznikov et al (2007) have shown that extracellular glutamate levels are enhanced by stress in the amygdala, and this too is reversed by tianeptine. Thus, excess glutamate and its electrophysiological actions on receptors that trigger plasticity are both targeted by tianeptine in the amygdala.…”

“…The atypical antidepressant tianeptine is reported to be remarkably effective in preventing many of these stress effects on structural and physiological markers of plasticity, including those involving glutamatergic transmission (Kole et al, 2002;Qi et al, 2009;Reagan et al, 2004;Reznikov et al, 2007;Vouimba et al, 2006;Watanabe et al, 1992). Therefore, we first investigated the effects of tianeptine on EPSCs mediated by a-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs).…”

Reflections on worker’s compensation in the state of New Jersey

“…Depression impairs cognition through stress-induced alterations in the morphology and metabolism of the hippocampus in the brain. 19,20 Regression, which is a retreat from an achieved level of mature adaptation, is a major threat to the injured worker's recovery. Regression commonly occurs in frightened people who do not have a strong support system.…”