title: Stress, glucocorticoids and glutamate release: effects of antidepressant drugs.
abstract: Stressful life events impact on memory, cognition and emotional responses, and are known to precipitate mood/anxiety disorders. It is increasingly recognized that stress and its neurochemical and endocrine mediators induce changes in glutamate synapses and circuitry, and this in turn modify mental states. Half a century after the monoamine hypothesis, it is widely accepted that maladaptive changes in excitatory/inhibitory circuitry have a primary role in the pathophysiology of mood/anxiety disorders. The neuroplasticity hypothesis posits that volumetric changes consistently found in limbic and cortical areas of depressed subjects are in good part due to remodeling of neuronal dendritic arbors and loss of synaptic spines. A considerable body of work, carried out with in vivo microdialysis as well as alternative methodologies, has shown that both stress and corticosterone treatment induce enhancement of activity-dependent glutamate release. Accordingly, results from preclinical studies suggest that stress- and glucocorticoid-induced enhancement of glutamate release and transmission plays a main role in the induction of maladaptive cellular effects, in turn responsible for dendritic remodeling. Additional recent work has showed that drugs employed for therapy of mood/anxiety disorders (antidepressants) prevent the enhancement of glutamate release induced by stress. Understanding the action of traditional drugs on glutamate transmission could be of great help in developing drugs that may work directly at this level.
authors.affiliation: Center of Neuropharmacology, Department of Pharmacological Sciences, University of Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Musazzi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D005938:Glucocorticoids / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D013315:Stress, Psychological
chemical_list: D000928:Antidepressive Agents; D005938:Glucocorticoids; D018698:Glutamic Acid