It is not known, however, if noradrenergic modulatory function is

It is not known, however, if noradrenergic modulatory function is compromised by chronic stress, perhaps contributing to the stress-induced cognitive deficit. Thus, the first study investigated whether acutely elevating noradrenergic activity in mPFC still enhances cognitive function after chronic stress. As previously demonstrated, CUS impaired cognitive set-shifting on the AST.

This deficit was abolished by acute systemic administration of the alpha(2)-adrenergic autoreceptor antagonist, atipamezole. Microdialysis revealed no differences in extracellular norepinephrine (NE) levels in mPFC of CUS-exposed and unstressed control rats at baseline or during behavioral testing, and comparable increases after atipamezole. In the second experiment, rats were treated chronically with the selective NE reuptake MDV3100 ic50 blocker, desipramine, during the CUS treatment through behavioral testing. Again. CUS impaired cognitive set-shifting Verubecestat in vehicle-treated rats, and chronic desipramine treatment prevented

such deficits. Acute blockade of post-synaptic alpha(1)-adrenergic receptors in mPFC prior to testing blocked the beneficial effect of desipramine on cognitive set-shifting. These results suggest that desipramine restores cognitive set-shifting capability that has been compromised by chronic stress by activating alpha(1)-adrenergic receptors in the mPFC. Thus, noradrenergic modulatory capability in mPFC remains intact after CUS, and this represents one possible substrate by which antidepressants may exert their beneficial effects in the treatment

of depression. (C) 2010 Elsevier Inc. All rights reserved.”
“Chronic psychosocial isolation stress (CPSI) modulates glucocorticoid receptor else (GR) functioning in Wistar male rat hippocampus (HIPPO) through alteration of nuclear GR phosphorylation and its upstream kinases signaling, which parallels animal depressive-like behavior. The current study investigated potential gender specificities regarding the effect of chronic therapy by an antidepressant fluoxetine (FLU) on GR signaling in HIPPO and depressive-like behavior in CPSI animals.

FLU was administrated to female and male naive or CPSI rats for 21 days and GR protein, its phosphorylation status and upstream kinases, as well as GR and BDNF mRNA were followed in HIPPO together with animal serum corticosterone (CORT) and depressive-like behavior.

The results showed that CPSI increased immobility in males versus hyperactivity in females and disrupted nuclear pGR232-Cdk5 pathway and JNK signaling in a gender-specific way. In contrast, in both genders CPSI increased the nuclear levels of GR and pGR246 but decreased CORT and mRNA levels of GR and BDNF.

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