Slow release administration of metoclopramide in an attempt to raise plasma prolactin concentration in sheep : a dissertation submitted in partial fulfilment of the requirements for the degree of Bachelor of Agricultural Science (Honours) at Lincoln University

Animal and pasture productivity is known to be altered by the infection of perennial ryegrass (Lolium perenne L) pastures with the endophytic fungus Acremonium loliae. Animals grazing these pastures have reduced live weight gains, lowered plasma prolactin and testosterone concentrations and increased faecal soiling. Recent research has started to focus on the use of the drug metoc1opramide (MCP) which raises plasma prolactin concentrations. Raising plasma prolactin concentrations may alleviate some of the symptoms of ryegrass staggers (RGS) in infected animals and reduce production losses associated with RGS. Slow release devices containing MCP may provide a slow sustained release of MCP resulting in a continually elevated plasma prolactin concentration. The experiment consisted of three trials utilizing a different slow release device in each trial. Trial One ran from 14 April to 8 May 1992, a total of 24 days. Thirty-two coopworth ewes were randomly assigned to four treatment groups (n=8). Animals were grazed on a lucerne pasture. Blood samples were collected on days 0, 2, 3, 6, 11, 14, 15, 19 and 24. Silicone rubber tubing implants containing MCP (0, 200, 1000, 5000 mg) were implanted on day 2 and removed on day 14. Blood plasma samples were analysed for prolactin concentration. Trial Two ran from 17 to 22 August 1992. Eight coopworth ewes were housed indoors. Four implants made of MCP and calcium lactate in a ratio of 1:1 were implanted into four animals. Sham implants (100% calcium lactate) were implanted into the remaining four animals. Visual observation of the surgical site suggested tablet removal was not necessary. Trial Three ran for 9 days from 2 to 11 September 1992. Four of eight ewes received subcutaneous implants of alginic acid. These were removed 9 days later and any evidence of tissue reaction noted. An in vitro trial was conducted using eight alginic acid implants. Four implants contained MCP the remaining four implants were controls. The implants were placed in saline solution and incubated in a shaking water bath at 37 °C. Absorbance of the saline samples was measured daily using a UV spectrophotometer. The success of slow release delivery of MCP using these devices was limited. There was no effect of treatment on plasma prolactin concentration in Trial 1. Release of MCP through the silicone rubber was prevented due to the polar nature of MCP. Tablet dissolution in Trial Two was rapid (within 24 hours) but a fibrotic reaction developed in response to calcium lactate. The alginic acid implants of Trial Three caused no tissue reaction in animals. The in vitro trial showed that MCP was released for up to 48 hours, thereafter no further increase in MCP was detected. Prolonged subcutaneous release of MCP in sheep using various devices was investigated with limited success