کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5558028 | 1561016 | 2017 | 9 صفحه PDF | دانلود رایگان |
- Classical and non-classical antidepressants revert soluble βA-induced depressive phenotype in rats.
- Fluoxetine reverts soluble βA-induced depressive phenotype with a specific “βA-lowering” effect.
- The non-classical antidepressant ketamine holds neuroprotective properties towards soluble βA-induced toxicity.
Mounting evidence suggests that depression represents a risk factor and an early manifestation of Alzheimer's disease (AD). Neuropsychiatric symptoms may derive from neurobiological changes in specific brain areas and may be considered prodromal of dementia. We have previously reported the depressive-like profile in rats receiving a single intracerebroventricular injection of soluble amyloid beta protein (ÃA). Here, we verified the effect of different classes of antidepressants on the ÃA-induced depressive behavior and on cortical monoamine levels. To these purposes, the forced swimming test was performed and cortical levels of serotonin (5-HT) and noradrenaline (NA) were quantified by high performance liquid chromatography (HPLC). We found that acute fluoxetine (20 mg/kg, s.c.), reboxetine (10 mg/kg, s.c.), and ketamine (15 mg/kg, i.p.) significantly reduced the immobility in ÃA-treated rats compared to controls. Fluoxetine and reboxetine reversed 5-HT reduction, while βA-induced NA increase was further enhanced by all treatments. Treatments with fluoxetine, reboxetine and ketamine were able to revert soluble ÃA-induced decrease of cortical BDNF levels, while only fluoxetine and ketamine, but not reboxetine, had the same effects on cortical NGF expression. Moreover, plasma soluble ÃA-levels were lowered by fluoxetine, but not reboxetine and ketamine, treatments.Our data suggest that different classes of antidepressants yield a short-acting effect on rat soluble ÃA-induced depressive profile. Thus, we hypothesize a novel common mechanism of action of these drugs also based upon a “ÃA lowering” effect. Although further investigations are still needed, our study might open a new scenario for unravelling the molecular antidepressant mechanisms of these drugs.
Journal: Progress in Neuro-Psychopharmacology and Biological Psychiatry - Volume 78, 1 August 2017, Pages 114-122