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

REASONS FOR PERFORMING THE STUDY: Increased plasma progestagen concentrations have been reported in foals with neonatal maladjustment syndrome (NMS). These steroids may cross the blood-brain barrier and have dampening effects in the central nervous system.
OBJECTIVES: To evaluate if the infusion of a progesterone derivative (allopregnanolone) in a healthy neonatal foal would induce clinical signs compatible with NMS.
METHODS: A healthy neonatal foal from a healthy mare with a normal gestation (length, no complications), birth and placenta was infused with allopregnanolone to observe its neurobehavioural effects. Heparinised blood samples were collected pre- and post infusion to determine various progestagen concentrations using liquid chromatography mass spectrometry. A second healthy neonatal foal was infused with ethanol and saline for comparison of clinical observations.
RESULTS: Infusion of allopregnanolone resulted in obtundation, lack of affinity for the mare and decreased response to external stimuli. These effects were short-lasting and associated with measurable concentrations of progestagens. CONCLUSIONS AND POTENTIAL RELEVANCE: Infusion of a steroid metabolite to a healthy neonatal foal resulted in neurobehavioural alterations compatible with those observed in foals with NMS. These findings suggest that increased progestagen concentrations may be responsible for some of the behavioural changes observed in foals with NMS.