Agalactia or hypogalactia in a postpartum bitch may pose serious risks to health of the neonates. When puppies do not ingest a sufficient amount of colostrum within the first 16 to 24 hours after birth, failure of passive immune transfer occurs, which affects their growth and survival.1,2 If neonates are not adequately nourished, they are at high risk of fading or developing sepsis, and they may die soon after birth. Primary agalactia or hypogalactia is extremely rare and is associated with anatomic abnormalities of the mammary glands or a lack of response to physiologic stimuli.3 In cases of secondary hypogalactia, milk production is decreased as a result of concurrent disease of the dam (eg, metritis or mastitis). Furthermore, hypocalcemia, stress (eg, Cesarean section), premature parturition, or undernourishment of a bitch may lead to insufficient milk yield.3 Certain drugs or hormones (eg, slow-release deslorelin implants or cabergoline) administered during pregnancy or lactation may also negatively influence milk production.4–6
Prolactin is essential for mammary gland development and initiation and maintenance of lactation.7–9 It is a polypeptide hormone produced by lactotroph cells of the anterior pituitary gland.10 The most important regulator of prolactin secretion is dopamine, which is produced by the hypothalamus and exerts tonic inhibition.9 Prolactin secretion is stimulated by several substances and hormones (eg, estradiol, thyrotrophinreleasing hormone, oxytocin, vasoactive intestinal peptide, serotonin, opioid peptides, and angiotensin II).9,11–13 In bitches, there is a substantial increase in serum prolactin concentration 16 to 56 hours prior to parturition, which reaches peak concentrations approximately 8 to 32 hours before birth.14,15 Prolactin concentrations decrease to concentrations similar to or less than prepartum concentrations during the first 24 to 48 hours after parturition, but then increase again to a secondary peak on day 10 after parturition.14,15 Plasma prolactin concentrations are high during lactation, with large variations within and among individual bitches,14,15 which may be partly attributable to the circadian rhythm of prolactin concentrations.5 Prolactin stimulates α-lactalbumin production,9,16,17 which is the regulatory subunit of the lactose synthase complex within the mammary gland.18,19 Lactose, through its osmotic actions, is the major determinant of the aqueous portion and thus the volume of milk.20 Milk lactose concentration increased in Beagle bitches from 3.47% at 7 to 9 days after parturition to 4.13% at 29 to 30 days after parturition, but none of the other milk constituents differed over time.21 Similarly, lactose concentration in canine milk was found to increase in the first 5 days of lactation22 or until 2 weeks after parturition.23
Milk lactose concentration and milk volume increased significantly after administration of recombinant human prolactin to women with prolactin deficiency and lactation insufficiency.24 Increased prolactin concentrations and galactorrhea are adverse effects reported for the administration of metoclopramide, which is an antidopaminergic gastrointestinal prokinetic used for the prevention and treatment of signs of nausea and vomiting.25,26 Therefore, metoclopramide is used as a galactogogue in human medicine to increase milk production.27,28 In puerperal women with term or premature infants and that had or did not have lactational insufficiency, daily doses of 30 or 45 mg of metoclopramide significantly increased serum prolactin concentrations, milk yield, or both29–34; the higher dose resulted in a more rapid onset of effects.29 However, the same daily dose (30 mg of metoclopramide) failed to augment milk production in women with premature newborns in other studies.35,36 A single injection of metoclopramide (0.4 mg/kg, IV) to healthy anestrous bitches resulted in a significant transient increase in serum prolactin concentrations.37 Administration of metoclopramide (0.2 mg/kg, PO, q 8 h) to male Beagles significantly increased the mean ± SD prolactin concentration from 4.5 ± 1.1 ng/mL to 6.5 ± 1.6 ng/mL.38 This indicates that pituitary prolactin secretion in dogs is modulated by the administration of dopamine D2 receptor antagonists. Although the use of metoclopramide to treat agalactia or hypogalactia in bitches because of its prolactin-stimulating actions is anecdotal and lacking scientific evidence, there are various protocols that recommend metoclopramide at lower dosages ranging from 0.1 to 0.2 mg/kg or 0.2 to 0.5 mg/kg every 6 to 8 or 8 to 12 hours3,39–41 or at higher dosages from 1 to 5 mg/kg every 6 to 8 hours,40 administered SC or PO. However, the clinical efficacy of these regimens has not been confirmed in a controlled study.
The effects of galactogogues on milk yield and maternal prolactin concentrations have been widely studied, but their influence on milk composition is not well known. In women with full-term newborns, metoclopramide did not alter milk prolactin and sodium concentrations34 and did not influence total fat, dry matter, fat-free dry matter, and total nitrogen content of milk, but it did promote the shift from colostrum to mature milk.30 Domperidone, another antidopaminergic gastrointestinal prokinetic that has been used in humans as a galactogogue, increased yield as well as carbohydrate and calcium content of preterm human milk, compared with results of a placebo treatment.42 To the authors' knowledge, the influence of metoclopramide administration on milk composition of dogs has not been studied.
The objective of the study reported here was to investigate the effect of metoclopramide on serum prolactin concentrations and milk lactose and energy content in bitches during early lactation. Milk lactose concentration and weight gain of puppies were determined to estimate the treatment effect on milk production.
The authors declare that there were no conflicts of interest.
Body condition score
Sodium acetate NaOH Sodium hydroxide
Paspertin, BGP Products GmbH, Baar, Switzerland.
IKA calorimeter C2000 basic, IKA-Werke GmbH, Staufen, Germany.
HPAEC-PAD, ICS3000, Thermo Fisher Scientific, Sunnyvale, Calif.
CarboPac PA1, Thermo Fisher Scientific, Sunnyvale, Calif.
SPSS Statistics for Windows, version 22.0, IBM Corp, Armonk, N Y.
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