A single dose of ketamine cannot prevent protracted stress-induced anhedonia and neuroinflammation in rats.
Rodrigo Moraga-AmaroCyprien G J GuerrinLuiza Reali NazarioBruno Lima GiacobboRudi A J O DierckxJimmy StehbergErik F J de VriesJanine DoorduinPublished in: Stress (Amsterdam, Netherlands) (2022)
Worldwide, millions of people suffer from treatment-resistant depression. Ketamine, a glutamatergic receptor antagonist, can have a rapid antidepressant effect even in treatment-resistant patients. A proposed mechanism for the antidepressant effect of ketamine is the reduction of neuroinflammation. To further explore this hypothesis, we investigated whether a single dose of ketamine can modulate protracted neuroinflammation in a repeated social defeat (RSD) stress rat model, which resembles features of depression. To this end, male animals exposed to RSD were injected with ketamine (20 mg/kg) or vehicle. A combination of behavioral analyses and PET scans of the inflammatory marker TSPO in the brain were performed. Rats submitted to RSD showed anhedonia-like behavior in the sucrose preference test, decreased weight gain, and increased TSPO levels in the insular and entorhinal cortices, as observed by [ 11 C]-PK11195 PET. Whole brain TSPO levels correlated with corticosterone levels in several brain regions of RSD exposed animals, but not in controls. Ketamine injection 1 day after RSD disrupted the correlation between TSPO levels and serum corticosterone levels, but had no effect on depressive-like symptoms, weight gain or the protracted RSD-induced increase in TSPO expression in male rats. These results suggest that ketamine does not exert its effect on the hypothalamic-pituitary-adrenal axis by modulation of neuroinflammation.
Keyphrases
- weight gain
- stress induced
- pet imaging
- pain management
- cerebral ischemia
- body mass index
- birth weight
- traumatic brain injury
- lipopolysaccharide induced
- resting state
- computed tomography
- major depressive disorder
- end stage renal disease
- depressive symptoms
- lps induced
- white matter
- cognitive impairment
- ejection fraction
- healthcare
- chronic kidney disease
- poor prognosis
- pet ct
- positron emission tomography
- bipolar disorder
- mental health
- newly diagnosed
- oxidative stress
- subarachnoid hemorrhage
- endothelial cells
- sleep quality
- multiple sclerosis
- prognostic factors
- physical activity
- blood brain barrier
- inflammatory response
- binding protein
- diabetic rats
- contrast enhanced
- sensitive detection