Development of an estradiol-dopamine anagonist protocol for inducing ovulation in seasonally anovulatory mares

Five experiments were conducted to assess potential improvements in a protocol for inducing ovulation in seasonally anovulatory mares based upon estradiol pretreatment followed by dopamine antagonist injection. The first experiment compared various doses of estradiol cypionate (ECP) and domperidone (in biodegradable microparticles), as well as additions and deletions to the protocol. It was concluded that as little as 75 mg ECP and as little as 1.5 g of domperidone could be used with success, but that both components were required. In the second experiment, timing of the injection (1, 6, or 11 days apart) and ECP dose were assessed. It was concluded that administration of domperidone 1 day after ECP injection provided the best results, and that 50 and 100 mg ECP provided similar results. The third experiment, using geldings as a model for prolactin secretion, compared the prolactin responses to an alternate dopamine antagonist, sulpiride, to those with domperidone, both in biodegradable particles. The magnitude of the prolactin responses were similar for both antagonists, however the sulpiride effect was quicker to occur (1 day) and was shorter-lived (\u3c10 days) than that of domperidone (about 18 days). In the fourth experiment, two doses of ECP (25 and 50 mg) were compared followed immediately (same day) by injection of domperidone or sulpiride in biodegradable microparticles. Both the luteinizing hormone (LH) and prolactin responses to treatment were poor or absent in all but a few mares, and only two mares had early ovulation (one control mare and one mare receiving 25 mg ECP and domperidone). The reason for the poor responses was unknown, but the experiment confirmed the need for responses in LH and prolactin for positive ovarian responses. The last experiment evaluated domperidone versus a new non-particle formulation of sulpiride given at two doses (0.75 versus 1.5 g) on days 1, 6, and 11 relative to ECP (100 mg). Also factored across those treatments was the administration of 50 mg thyroxin in microparticles administered 6 days before ECP injection. High success rates (prolactin and ovulation) were obtained with the higher sulpiride dose. Thyroxin treatment had no effect