Background: Ionizing radiation (IR) is one of the major limiting factors for human deep-space missions. Preventing IR-induced cognitive alterations in astronauts is a critical success factor. It has been shown that cognitive alterations in
rodents can be inferred by alterations of a psycho-emotional balance, primarily an anxiogenic effect of IR. In our recent
work we hypothesized that the neurokinin-1 (NK1) receptor may be instrumental for such alterations.
Objective: The NK1 receptor antagonist rolapitant and the classic anxiolytic diazepam (as a comparison drug) were selected
to test this hypothesis on Wistar rats.
Method: Pharmacological substances were administered through intragastric probes. We used a battery of tests for a comprehensive ethological analysis. A high-performance liquid chromatography was applied to quantify monoamines content. An
analysis of mRNA expression was performed by real-time PCR. Protein content was studied by Western blotting technique.
Results: Our salient finding includes no substantial changes in anxiety, locomotor activity and cognitive abilities of treated
rats under irradiation. No differences were found in the content of monoamines. We discovered a synchronous effect on
mRNA expression and protein content of 5-HT2a and 5-HT4 receptors in the prefrontal cortex, as well as decreased content
of serotonin transporter and increased content of tryptophan hydroxylase in the hypothalamus of irradiated rats. Rolapitant
affected the protein amount of a number of serotonin receptors in the amygdala of irradiated rats.
Conclusion: Rolapitant may be the first atypical radioprotector, providing symptomatic treatment of CNS functional disorders in astronauts caused by IR.