A single dose of ketamine cannot prevent protracted stress-induced anhedonia and neuroinflammation in rats.

Abstract

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 [11C]-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.

• Authors: Rodrigo Moraga-Amaro, Cyprien G J Guerrin, Luiza Reali Nazario, Bruno Lima Giacobbo, Rudi A J O Dierckx, Jimmy Stehberg, Erik F J de Vries, Janine Doorduin
• Journal: Stress (Amsterdam, Netherlands) (Stress) Vol. 25 Issue 1 Pg. 145-155 (01 2022) ISSN: 1607-8888 [Electronic] England
• PMID: 35384793 (Publication Type: Journal Article)

Chemical References

• Antidepressive Agents
• Carrier Proteins
• Receptors, GABA
• Receptors, GABA-A
• Tspo protein, rat
• Ketamine
• Corticosterone

Topics

• Anhedonia
• Animals
• Antidepressive Agents (pharmacology)
• Carrier Proteins
• Corticosterone
• Depression (metabolism, prevention & control)
• Disease Models, Animal
• Hypothalamo-Hypophyseal System (metabolism)
• Ketamine (pharmacology)
• Male
• Neuroinflammatory Diseases
• Pituitary-Adrenal System (metabolism)
• Rats
• Receptors, GABA (metabolism)
• Receptors, GABA-A
• Stress, Psychological (metabolism)
• Weight Gain