Acute stress-mediated increases in extracellular glutamate levels in the rat amygdala: differential effects of antidepressant treatment.
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.
Reznikov
Leah R
LR
Department of Pharmacology, Physiology and Neuroscience, School of Medicine, University of South Carolina, 6439 Garners Ferry Rd, D40 Columbia, SC 29208, USA.
Grillo
Claudia A
CA
Piroli
Gerardo G
GG
Pasumarthi
Ravi K
RK
Reagan
Lawrence P
LP
Fadel
Jim
J
D000208:Acute Disease / Q000628:therapy; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D013841:Thiazepines / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D026941:Sodium Channel Blockers; D013841:Thiazepines; D005473:Fluoxetine; C050504:tianeptine; D018698:Glutamic Acid