Dopamine and Its Evil Twin Ergovaline

In the horse, the hormone dopamine exerts a number of effects through its actions on the pituitary gland. Both dopamine and ergovaline, a dopaminergic agonist (a drug that stimulates dopamine receptors), can significantly impact the mare's reproductive cycle, said Valerie J. Linse, MS, DVM, of Hagyard Equine Medical Institute, during her presentation at the Hagyard Bluegrass Equine Reproduction Symposium 2006, which was held Oct. 18-21 in Lexington, Ky. The effects of dopamine deficiency can be observed in horses with pituitary pars intermedia dysfunction (PPID or Cushing's disease), while the effects of a relative dopamine excess are evident in cases of fescue toxicosis.

Pituitary pars intermedia dysfunction is the most common equine endocrinopathy (disorder of the endocrine gland). While the disease isn't fully understood, research suggests that it occurs as a result of a dopamine deficiency at the level of the pituitary. The resulting decrease in dopamine inhibition leads to a loss of circadian rhythm and chronically elevated cortisol levels. 

Pituitary pars intermedia dysfunction is most frequently diagnosed in horses older than 15 years of age. Typical signs of the condition include muscle wasting, hirsutism (characterized by a long, often curly hair coat that does not shed out well), and obesity. Horses with PPID are predisposed to chronic laminitis, parasitic and bacterial infections, and infertility.

While the dexamethasone suppression test has long been the gold standard for diagnosing the condition, its safety and repeatability have been questioned. According to Linse, "The reliability of the dexamethasone suppression test may be overestimated. In addition, it has the potential to exacerbate laminitis."

Although other diagnostic tests for PPID exist, all tests have a significant seasonal limitation. Due to a seasonal increase in the production of á-melanocyte stimulating hormone by the intermediate pituitary, all tests that are conducted in the fall of the year may lead to false positive results.

Treatment with the dopamine agonist pergolide has resulted in improvement of clinical signs in 85% of horses diagnosed with PPID, according to a study completed at the University of Pennsylvania and published in 2002.

Proper hoof care and a diet low in soluble carbohydrates can reduce secondary complications, including laminitis and hyperinsulinemia.

The effects of excess dopamine are evident in cases of fescue toxicosis, a syndrome that develops when pregnant mares ingest tall fescue infested with the endophyte Neotyphdium coenophialum. Although the endophyte improves the hardiness of tall fescue, it also produces the toxin ergovaline, a dopamine agonist which binds tightly to specific dopamine receptors (called D2 receptors) in the anterior (toward the front) pituitary.

"In pregnant mares, clinical signs of fescue toxicosis may include agalactia (the absence of milk production), prolonged gestation, dystocia, placental edema, and red bag (presentation of the placenta before the foal)," said Linse. "Abortion and still birth occur in 50-86% of cases (values that were first reported in a 1988 study on the effects of endophyte-contaminated fescue on performance and reproduction of mares)."

Prevention of fescue toxicosis relies on eradicating tall fescue from pastures and by removing pregnant mares from tall fescue pastures at least 30 days prior to expected parturition. Fescue toxicosis can be successfully treated in late-term pregnant mares with domperidone, a dopamine antagonist that selectively binds to D2 dopamine receptors. Through competitive binding, domperidone prevents ergovaline from interacting with the D2 receptors, and consequently inhibits the effects of dopamine and dopamine agonists on the anterior pituitary. When administered to mares daily beginning 30 days prior to parturition, domperidone has been shown to effectively reduce the adverse effects of ergovaline on the fetus, placenta, and mare.

About the Author

Rallie McAllister, MD

Rallie McAllister, MD, grew up on a horse farm in Tennessee, and has raised and trained horses all of her life. She now lives in Lexington, Ky., on a horse farm with her husband and three sons. In addition to her practice of emergency and corporate medicine, she is a syndicated columnist (Your Health by Dr. Rallie McAllister), and the author of four health-realted books, including Riding For Life, published by Eclipse Press and available at or by calling 800/582-5604.

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