Effects of metoclopramide and quipazine on serum prolactin concentrations in steers.

The dopamine antagonist metoclopramide monohydrochloride (MC) and the serotonin agonist quipazine maleate (Q) were administered to steers by both the oral and intravenous (i.v.) routes. Dose-response studies were designed to determine the effects of these drugs on serum prolactin (PRL) concentrations. Parameters subjected to analysis included maximal serum PRL concentrations within 1 h and the areas under the PRL response curves over time. At 1, 4, and 8 mg/kg i.v., and at 15, 30, 45, and 60 mg/kg orally, MC increased (P less than 0.05) serum PRL concentrations (difference between maximal and basal serum PRL concentrations) and increased (P less than 0.05) areas under the PRL response curves except for 1.0 mg/kg i.v. Doses of MC greater than 60 mg/kg and Q at all dosage rates were considered toxic. These studies determined a dose-response to MC in terms of serum PRL concentration and indicate that MC is well tolerated and effective for elevating serum PRL concentrations in steers. Furthermore, 4 mg/kg i.v. and 15 mg/kg orally could be considered the preferred dosage rates due to a plateau in the response above those rates.

Neuroendocrine measurements in steers grazed on endophyte-infected fescue.

Dopamine (DA), serotonin (5HT) and selected precursors and metabolites were measured in the anterior pituitary gland, hypothalamus and pineal gland, along with serum prolactin (PRL) and average daily gains (ADG), in steers (n = 6/group) grazing endophyte (Acremonium coenophialum)-infected and noninfected fescue (Festuca arundinacea Schreb). Paddocks (two/treatment) were designated 100F and 0F (100 and 0% infection, respectively). After 6 wk, three animals from one of the 100F paddocks were exchanged with three animals from one of the 0F paddocks, yielding 0F, 100F/0F, 0F/100F and 100F groups (n = 3). Compared to 0F steers, 100F steers had reduced serum PRL (9.23 vs 32.55 ng/ml, P less than or equal to .0001) and trial ADG (-.07 vs .28 kg, P less than or equal to .0002) but increased pituitary dihydroxyphenylacetic acid (DOPAC, a major metabolite of DA; 108 vs 59 ng/g, P less than or equal to .02) and 5-hydroxyindoleacetic acid (5HIAA, a major metabolite of 5HT; 265 vs 148 ng/g, P less than or equal to .04). Pituitary 5HIAA was greater in the steers rotated from the 0F to 100F paddocks than in steers maintained on the 0F paddocks (296 vs 148 ng/g, P less than or equal to .04). In addition pineal 5-hydroxytryptophan (5HTP, a precursor of 5HT) was increased (502 vs 280 ng/ml; P less than .08), whereas 5-methoxyindoleacetic acid (MIAA, a major metabolite of 5HIAA) and the 5HT/5HTP ratio were reduced (P less than .07) in 100F vs 0F steers. No differences among the treatment groups were observed in hypothalamic neurotransmitter and metabolite concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of metoclopramide on steers grazing endophyte-infected fescue.

The dopamine antagonist metoclopramide (MC) was administered to steers grazing on endophyte-infected fescue. Yearling Angus steers (n = 24) were assigned randomly to pasture treatments including high (74%) and low (33%) endophyte levels and low (134 kg N.ha-1.yr-1) and high (335 kg N.ha-1.yr-1) N fertilization rates. One steer of the pair in each paddock (n = 12) received MC, whereas the other received sucrose (S) (15 mg/kg body weight, orally, three times a week for 10 wk). Blood for basal and maximal TRH-stimulated serum prolactin (PRL) concentrations was obtained before animals grazed fescue, after grazing for 1 mo, and after 3, 6 and 9 wk of animal treatment. Grazing endophyte-infected fescue decreased (P less than .05) basal serum PRL concentrations (less than 1.0 vs 5.3 ng/ml, high vs low endophyte). Basal serum PRL increased after 3, 6 and 9 wk of MC treatment (58.1 vs 5.4, 46.0 vs 12.0 and 50.8 vs 16.9 ng/ml, MC vs sucrose, respectively). After 6 wk of animal treatments, MC increased (P less than .05) serum cholesterol (84.7 vs 60.8 mg/dl, MC vs S). Animals treated with MC spent more (P less than .05) time between 1200 and 1600 grazing (22.4% vs 6.2%, MC vs S respectively) and had faster ADG (.314 vs .150 kg/d, MC vs S). The results implicate dopaminergic processes in fescue toxicosis.

Quipazine-metoclopramide inhibition of CB-154-induced prolactin suppression in rats: neurotransmitter-metabolite correlations.

The ability of quipazine and metoclopramide to protect rats from CB-154-induced suppression of serum prolactin concentrations was studied. These drugs affect whole brain concentrations of dopamine and serotonin, and their major metabolites dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid. Serum prolactin concentrations have been correlated with the concentrations of the neurotransmitters and their respective metabolites. Differences in the metabolite/precursor ratios have been used to compare turnover rates of the neurotransmitters dopamine and serotonin. Increased turnover of dopamine and decreased turnover of serotonin correlate with elevated prolactin concentrations for quipazine and metoclopramide administered together. The combination of quipazine and metoclopramide protects rats against CB-154-induced prolactin suppression better than either of the drugs given alone. This study suggests that a quipazine-metoclopramide regimen may have therapeutic potential for combating ergotlike fescue and other similar toxicities observed in cattle grazing on endophyte-infected pasture grasses.

Effect of clonidine, quipazine, and LY 53857 on the prolactin-suppressant action of bromocriptine in rats.

The alpha 2-adrenergic agonist clonidine hydrochloride, the serotonin agonist quipazine maleate, and the serotonin (5-HT2) antagonist LY 53857 were tested alone and in various combinations for their capabilities to increase mean serum prolactin (MSP) concentrations in rats given the synthetic ergot alkaloid CB-154 (2-bromo-alpha-ergocriptine), a known prolactin suppressor. The LY 53857 and the combination of clonidine, quipazine, and LY 53857 significantly decreased MSP concentrations. Quipazine given alone (10 mg/kg of body weight) was best able to increase MSP concentration and has potential to antagonize prolactin-depressant effects of ergot alkaloids.