Effect of the dipeptide BDNF mimetic (compound GSB-106) on reflex development and monoamine levels in Wistar rats with an experimental autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental condition accompanied by alterations in serotonergic, dopaminergic, and noradrenergic systems, as well as delays in early psychomotor and sensorimotor development. One possible approach to correcting these disturbances is the use of BDNF mimetics that regulate synaptic plasticity and neurogenesis. The aim of this study was to investigate the effect of the low-molecular-weight dipeptide BDNF mimetic hexamethylenediamide bis(N-monosuccinyl-L-seryl-L-lysine) (GSB-106) on reflex development and monoamine content in the brain structures of Wistar rats with experimental ASD. The ASD model was induced by administration of sodium valproate (600 mg/kg) on gestation day 12.5. Offspring received GSB-106 orally at a dose of 0.1 mg/kg from postnatal day 7 to 21. The rate of sensorimotor reflex development was evaluated using the “Surface righting” and “Negative geotaxis” tests. Monoamines and their metabolites were quantified by high-performance liquid chromatography with electrochemical detection. GSB-106 improved negative geotaxis performance in both male and female rats with ASD (by 1.8–2.3 times), normalized NA and DOPAC levels in the frontal cortex of females, and reduced DA and 5-HT levels in male brain structures. Thus, GSB-106 exerts a normalizing effect on impaired early behavioral development and monoaminergic systems in rats with an ASD model, suggesting its potential as a promising compound for further investigation.

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