Inexpensive Medication Stimulates Early Ovulation in Mares

Patrick W. Concannon

For years, horse breeders have been trying to gain more control over the onset of their mares' breeding seasons. Although simulating increased day length with artificial lighting is a proven method for advancing the breeding season in winter-anestrous mares, it is expensive, time-consuming, and downright impractical for most breeders.

To perfect a new and simpler method that can advance reproductive function of mares by up to two months, Patrick W. Concannon, Ph.D., an endocrinologist, reproductive biologist, and expert on the effects of photoperiods in animals, is using Zweig funds to fine-tune the protocol for the use of the drug sulpiride. He is working in collaboration with Cornell equine reproductive specialist Peter F. Daels, D.V.M., Ph.D.

Currently, breeders use two methods to advance ovulation: artificial photoperiods or the experimental injection or implantation of a drug that costs up to $20 a day to administer. Sulpiride, however, costs only 75 cents per injection or $2.25 per oral dose.

Sulpiride inhibits the release of dopamine, a neurotransmitter hormone in the brain. Previously, Concannon and Daels had shown that, as in sheep, dopamine inhibits reproductive function and controls the non-breeding period in horses. By blocking the activity of dopamine with sulpiride, a so-called dopamine antagonist that has been widely used in humans to treat psychosis and in horses to treat fescue toxicity in pregnant mares, reproductive function was no longer inhibited and the mares' breeding cycles began early.

Initially, in 1994, they found that mares maintained outside and treated daily with sulpiride beginning in early February ovulated about 40 days earlier than untreated mares (on March 12 instead of April 20, on average).

"That was only 10 days later than mares kept indoors under artificial lighting for almost three months," Concannon says. In 1995, they repeated the experiment and found that treated mares ovulated about 20 days earlier than the controls. Concannon suggests that these poorer results were probably because of the exceptionally cold and wet winter that year.

Last year, Concannon switched to twice-daily doses of sulpiride with mares kept indoors under artificial lights beginning on Jan. 18. These mares started ovulating on February 3, on average, while untreated mares maintained outside did not start to ovulate until two months later, about April 1, on average.

With Zweig funding this year, Concannon is doing a much more comprehensive analysis by maintaining both treated and untreated mares indoors and outdoors. So far, the results have been dramatic. Mares maintained inside under an artificial photoperiod began ovulating within 14 to 24 days of starting sulpiride treatment on Jan. 18. They began ovulating on average on Feb. 5. The untreated animals kept indoors ovulated, on average, a month later, and much less synchronously. The treated mares had their first ovulations of the year within a 10-day period, while in the group of untreated mares, first ovulations occurred not only later but over a 40-day period.

"This Zweig-Funded study will allow us to not only make informed recommendations but also determine the role of dopamine in the regulation of seasonal reproduction in mares and the mechanism by which dopamine exerts its inhibitory effect."

With the animals maintained outside, sulpiride treatment beginning in mid-February appears to have had little or no effect this year, as they, like the untreated animals outside, had not ovulated by mid-April.

"Unfortunately, these outside animals were mares recently purchased at auction, and for which we have no breeding history," Concannon says. "Now we know that just being inside and given sulpiride has a clear advantage to being outside and treated with sulpiride. Mares that were treated with sulpiride and maintained inside under artificial photoperiods for only 12 to 22 days ovulated at the exact time when horse breeders would like to have their mares bred.

"Whether the greater effect of the sulpiride in animals kept indoors is due to warmer conditions or to the indoor lighting needs to be examined further," Concannon adds.

The study also is allowing the researchers to characterize the hormone activity in the mares as a way to show the specific effects of treatment. They are looking, for example, to see if the hormone prolactin is also involved in this aspect of the reproductive cycle.

"Strangely, prolactin can stimulate the ovaries in some species while it inhibits them in most others," Concannon says. "In previous studies, we've found that inhibiting prolactin secretion did not seem to affect the timing of ovulation in horses so we suspect that prolactin is not a mechanism at play here in horses. In contrast, we have shown in dogs that if we suppress prolactin secretion, we stimulate ovulation. In the mares, the hormone assays we do this spring, however, will determine if changes in another important hormone, follicle stimulated hormone, play an important role."

The research will also lead to more practical and specific protocols, including one using the oral administration of either sulpiride or perhaps a different dopamine antagonist.

"Since our preliminary results, we have received many inquiries from the veterinary community on the correct use of the dopamine antagonist for inducing reproductive function in mares," Concannon says. "This Zweig-funded study will allow us to not only make informed recommendations but also determine the role of dopamine in the regulation of seasonal reproduction in mares and the mechanism by which dopamine exerts its inhibitory effect.

"In the future, we should also be able to determine the relative roles of stimulatory photoperiod and increased temperature in the response to treatment and identify the most effective treatment protocol for advancing the breeding season in winter-anestrous mares."