title: Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus.
abstract: Increased vulnerability to aversive experiences is one of the main risk factors for stress-related psychiatric disorders as major depression. However, the molecular bases of vulnerability, on the one hand, and stress resilience, on the other hand, are still not understood. Increasing clinical and preclinical evidence suggests a central involvement of the glutamatergic system in the pathogenesis of major depression. Using a mouse paradigm, modeling increased stress vulnerability and depression-like symptoms in a genetically diverse outbred strain, and we tested the hypothesis that differences in AMPA receptor function may be linked to individual variations in stress vulnerability. Vulnerable and resilient animals differed significantly in their dorsal hippocampal AMPA receptor expression and AMPA receptor binding. Treatment with an AMPA receptor potentiator during the stress exposure prevented the lasting effects of chronic social stress exposure on physiological, neuroendocrine, and behavioral parameters. In addition, spatial short-term memory, an AMPA receptor-dependent behavior, was found to be predictive of individual stress vulnerability and response to AMPA potentiator treatment. Finally, we provide evidence that genetic variations in the AMPA receptor subunit GluR1 are linked to the vulnerable phenotype. Therefore, we propose genetic variations in the AMPA receptor system to shape individual stress vulnerability. Those individual differences can be predicted by the assessment of short-term memory, thereby opening up the possibility for a specific treatment by enhancing AMPA receptor function.
authors.affiliation: Research Group Neurobiology of Stress, Max Planck Institute of Psychiatry, 80804 Munich, Germany. mschmidt@mpipsykl.mpg.de
authors.forename: Mathias V
authors.initials: MV
authors.lastname: Schmidt
authors.forename: Dietrich
authors.initials: D
authors.lastname: Trümbach
authors.forename: Peter
authors.initials: P
authors.lastname: Weber
authors.forename: Klaus
authors.initials: K
authors.lastname: Wagner
authors.forename: Sebastian H
authors.initials: SH
authors.lastname: Scharf
authors.forename: Claudia
authors.initials: C
authors.lastname: Liebl
authors.forename: Nicole
authors.initials: N
authors.lastname: Datson
authors.forename: Christian
authors.initials: C
authors.lastname: Namendorf
authors.forename: Tamara
authors.initials: T
authors.lastname: Gerlach
authors.forename: Claudia
authors.initials: C
authors.lastname: Kühne
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.forename: Jan M
authors.initials: JM
authors.lastname: Deussing
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Müller
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D003865:Major Depressive Disorder / Q000209:etiology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005820:Genetic Testing / Q000379:methods*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007206:Individuality; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040081:Protein Array Analysis / Q000379:methods; D018091:Receptors, AMPA / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D055500:Resilience, Psychological / Q000187:drug effects; D012307:Risk Factors; D013315:Stress, Psychological / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D003345:Corticosterone; D018091:Receptors, AMPA; D013449:Sulfonamides; C430915:LY 404187; C104722:glutamate receptor ionotropic, AMPA 2