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High Exploratory Phenotype Rats Exposed to Environmental Stressors Present Memory Deficits Accompanied by Immune-Inflammatory/Oxidative Alterations: Relevance to the Relationship Between Temperament and Mood Disorders
- Source :
- Frontiers in Psychiatry, Frontiers in Psychiatry, Vol 10 (2019)
- Publication Year :
- 2019
-
Abstract
- Low-exploratory (LE) and high-exploratory (HE) rodents mimic human depressive and hyperthymic temperaments, respectively. Mood disorders (MD) may be developed by the exposure of these temperaments to environmental stress (ES). Psychiatric symptoms severity in MD patients is related to the magnitude of memory impairment. Thus, we aimed at studying the consequences of the exposure of LE and HE male Wistar rats, during periadolescence, to a combination of ES, namely, paradoxical sleep deprivation (PSD) and unpredictable stress (US), on anxiety-related behavior in the plus maze test, working (WM) and declarative memory (DM) performance. We also evaluated hippocampal immune-inflammatory/oxidative, as consequences of ES, and prevention of ES-induced alterations by the mood-stabilizing drugs, lithium and valproate. Medium exploratory (ME) control rats were used for comparisons with HE- and LE-control rats. We observed that HE-controls presented increased anxiolytic behavior that was significantly increased by ES exposure, whereas LE-controls presented increased anxiety-like behavior relative to ME-controls. Lithium and valproate prevented anxiolytic alterations in HE+ES rats. HE+ES- and LE+ES-rats presented WM and DM deficits. Valproate and lithium prevented WM deficits in LE-PSD+US rats. Lithium prevented DM impairment in HE+ES-rats. Hippocampal levels of reduced glutathione (GSH) increased four-fold in HE+ES-rats, being prevented by valproate and lithium. All groups of LE+ES-rats presented increased levels of GSH in relation to controls. Increments in lipid peroxidation in LE+ES- and HE+ES-rats were prevented by valproate in HE+ES-rats and by both drugs in LE+ES-rats. Nitrite levels were increased in HE+ES- and LE+ES-rats (five-fold increase), which was prevented by both drugs in LE+ES-rats. HE+ES-rats presented a two-fold increase in the inducible nitric oxide synthase (iNOS) expression that was prevented by lithium. HE+ES-rats showed increased hippocampal and plasma levels of interleukin (IL)-1β and IL-4. Indoleamine 2, 3-dioxygenase 1 (IDO1) was increased in HE+ES- and LE+ES-rats, while tryptophan 2,3-dioxygenase (TDO2) was increased only in HE+ES-rats. Altogether, our results showed that LE- and HE-rats exposed to ES present distinct anxiety-related behavior and similar memory deficits. Furthermore, HE+ES-rats presented more brain and plasma inflammatory alterations that were partially prevented by the mood-stabilizing drugs. These alterations in HE+ES-rats may possibly be related to the development of mood symptoms.
- Subjects :
- medicine.medical_specialty
Lithium (medication)
lcsh:RC435-571
memory impairment
Hippocampal formation
neuroinflammation
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
lcsh:Psychiatry
medicine
Memory impairment
Neuroinflammation
Original Research
unpredictable stress
Psychiatry
bipolar disorder
paradoxical sleep deprivation
biology
business.industry
animal model
Interleukin
Glutathione
temperament
medicine.disease
030227 psychiatry
Nitric oxide synthase
Psychiatry and Mental health
Endocrinology
chemistry
Mood disorders
biology.protein
business
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 16640640
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Frontiers in psychiatry
- Accession number :
- edsair.doi.dedup.....de5bd26494bce827b24b5092fba67105