Allopregnanolone infusion induced neurobehavioural alterations in a neonatal foal: is this a clue to the pathogenesis of neonatal maladjustment syndrome?

This study investigates if the hormone progesterone, specifically its derivative allopregnanolone, could be responsible for some of the behavioural changes seen in foals suffering from neonatal maladjustment syndrome (NMS). Infusion of allopregnanolone in a healthy newborn foal resulted in symptoms similar to NMS, suggesting that high levels of progesterone could be a contributing factor to the condition.

Objective and Method

• The research was undertaken to understand if the infusion of a progesterone derivative, specifically allopregnanolone, in a healthy newborn horse, could produce clinical signs similar to Neonatal Maladjustment Syndrome (NMS).
• To establish this connection, a healthy newborn horse, birthed from a healthy mare with a normal gestation period and no birth or placental complications, was infused with allopregnanolone.
• The neurological and behavioural effects of this infusion were then observed and documented.
• Blood samples from the foal were taken prior to and after the hormone infusion to ascertain different progestogen concentrations. This was done using liquid chromatography mass spectrometry, a process to identify individual chemicals and substances in a sample.
• For comparison, a second healthy newborn horse was infused with ethanol and saline. The clinical observations from both cases were then evaluated agaisnt each other.

Results

• The infusion of allopregnanolone in the first foal led to several changes in its behaviour, signalling possible signs of NMS. These included lack of energy (obtundation), reduced interest in its mother (lack of affinity for the mare) and a decreased response to external stimuli.
• These behavioural changes were temporary and were noted at the time of measurable concentrations of progestagens, hormones derived from progesterone.

Conclusions

• The behavioural changes observed post infusion mirrored the symptoms seen in foals afflicted with NMS, suggesting a connection between the two.
• The research indicates that an increase in progestagen concentrations could be a contributing factor for some of the behavioural changes observed in foals suffering from NMS.