Control of red fox (Vulpes vulpes) fertility with cabergoline: dose response and timing of intervention
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Reproduction (2001) 122, 147–154 Research
Control of red fox (Vulpes vulpes) fertility with cabergoline: dose
response and timing of intervention
C. A. Marks1, L. Jalkanen2, R. Savolainen2 and R. V. Short3
1Vertebrate Pest Research Department, Victorian Institute of Animal Science, PO Box 48,
Frankston, Victoria 3199, Australia; 2Department of Applied Zoology and Veterinary
Medicine, University of Kuopio, Kuopio, Finland; and 3Department of Obstetrics and
Gynaecology, University of Melbourne, Parkville, Victoria 3052, Australia
Cabergoline, a potent dopamine agonist and inhibitor of on days 35 and 48. Although lactation was not terminated in
prolactin secretion, was investigated as a potential fertility groups that received a single or double dose of cabergoline,
control agent in the red fox (Vulpes vulpes). Sixty silver fox increased post-natal cub mortality was associated with
vixens were selected randomly and artificially inseminated. cabergoline administration. Growth of cubs between 4 and
Cabergoline was fed to groups of 12 vixens in a minced 8 weeks of age was not inhibited in vixens that received
beef ration either as a single dose of 25, 50 or 100 µg kg–1, cabergoline. Doses of 100 µg cabergoline kg–1 administered
or a dose of 50 µg kg–1 that was repeated 2 days later each day from day 42 to day 46 resulted in abortions
(2 ⫻ 50 µg kg–1). Four foxes from each group of 12 were and terminated lactation. The capacity of single doses of
given cabergoline at day 28, day 35 or day 48 after artificial cabergoline to cause abortions in the red fox during
insemination, and a control group of four foxes was used as mid- rather than late pregnancy is contrary to reported
a comparison for each dose day. In a separate trial, two observations for the domestic dog. This finding indicates
groups of five foxes were selected randomly from the farm that luteotrophic support of the corpus luteum by prolactin
population and fed 100 µg kg–1 of either cabergoline or a may be more important at mid-pregnancy in the red fox.
placebo each day from day 42 to day 46 of pregnancy. The results of this study support previous field observations
Foxes that received single doses of cabergoline of that cabergoline delivered in bait affects the reproductive
100 µg kg–1 or 2 ⫻ 50 µg kg–1 aborted at day 28, but the success of vixens and may be a practical adjunct to the
same doses did not result in abortions when administered lethal control of wild red foxes in Australia.
Introduction current methods (Mansergh and Marks, 1993; Marks and
Short, 1996; Marks et al., 1996). Control of foxes by
Predation of wildlife by the introduced red fox (Vulpes
manipulating fertility may prevent population increase after
vulpes) is considered a major threat to the conservation of a
lethal control (Bomford, 1990; Bomford and O’Brien,
range of terrestrial wildlife species in Australia (Mansergh
1992), as well as the dispersal of foxes from urban habitats
and Marks, 1993; Saunders et al., 1995; Anon, 1996).
to rural areas containing susceptible wildlife species (Marks
Currently, management of fox populations is limited to the
and Short, 1996; Marks et al., 1996).
use of poison baiting with 1080 (sodium fluoroacetate),
Methods to reduce prolactin secretion induce abortions in
shooting, trapping and killing, exclusion fencing and den
domestic dogs (Canis familiaris) when administered after week
fumigation. Concerns over the potential impacts of 1080
6 of pregnancy (Conley and Evans, 1984; Post et al., 1988;
baiting on domestic and wildlife species such as quolls
Concannon et al., 1989; Jöchle et al., 1989; Olson et al.,
(Dasyurus maculatus) (Soderquist and Serena, 1993;
1989). In red foxes, inhibition of prolactin secretion is thought
Belcher, 1998), although not confirmed in some field
to cause luteal regression and abortion during the second
studies (King, 1989; McIlroy, 1993), currently limits the
half of pregnancy (Hartley et al., 1994). Cabergoline (1-[(6-
broad-scale use of baiting in some habitats. The conservation
allylergolin-8β-y1)carbonyl]-1-[3-(dimethylamino)propyl]-3
of some Victorian wildlife populations, including eastern
ethylurea) is a dopamine agonist with an extremely high
barred-bandicoots (Perameles gunni), little penguins
affinity for the dopamine receptor sites on the anterior
(Eudyptula minor) and mountain pygmy possums (Burramys
pituitary lactotrophs (Benedetti et al., 1990), and its
parvus), is compromised by foxes that inhabit adjacent
capacity to inhibit prolactin secretion is more potent
urban developments that are not easily managed with
than that of bromocriptine (Pontiroli et al., 1987; Dall’Ara
et al., 1988; Post et al., 1988; Caballero-Gordo et al., 1991;
Email: camarks@attglobal.net Rolland et al., 1991; Ferraro et al., 1992). Cabergoline
© 2001 Journals of Reproduction and Fertility
1470-1626/2001
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via free access148 C. A. Marks et al.
administration has been demonstrated to terminate or Oestrus was detected by monitoring the electrical
reduce lactation in the domestic dog (Jöchle et al., 1989). resistance of the vaginal tract using the probe method
The placement of baits containing cabergoline in proximity described by Møller et al. (1984a). After detection of
to natal dens during the breeding season significantly oestrus, vixens were artificially inseminated using freshly
reduced the reproductive success of vixens in an urban collected diluted semen as described by Fougner et al.
and rural field site (Marks and Short, 1996; Marks et al., (1973) and Fougner (1989). The duration of gestation in
1996) although it was impossible to conclude whether this wild red foxes is 52–53 days (Ryan, 1976; Lloyd, 1981;
was due to the termination of lactation, abortion or a Coman, 1983) and vixens usually whelped more than four
combination of both. Furthermore, the timing and dose of cubs, although litter sizes and mortality rates after birth vary
cabergoline that lead to abortion in red foxes is unknown. with different geographical locations (Voigt, 1987). In
The aim of the present study was to determine the dose and Finland, a national mean of 3.85 viable cubs per litter was
timing of cabergoline administration required to reduce the recorded from 2886 1-year-old vixens (Smeds, 1991).
reproductive success of the red fox. Between 1995 and 1998 at the Juankoski farm, a mean of
3.18 (SD = 1.47) and 4.47 (SD = 1.70) cubs per litter survived
2 weeks after whelping. The duration of gestation in vixens
Materials and Methods
during the same period was 52.8 (SD = 1.77) and 53.58
Study site and captive animals (SD = 1.48) days, respectively (Jalkanen, 1992).
Experiments were conducted at the Juankoski research
farm at the Department of Applied Zoology and Veterinary General procedures
Medicine, University of Kuopio (62⬚ 40’N 28⬚ 30’E),
Sixty vixens from the general farm population were
Finland. All procedures were approved by the Victorian
allocated randomly to either a treatment (n = 48) or a control
Institute of Animal Science Animal Ethics Committee as
group (n = 12) (Table 1). Typically, oestrus was detected
protocol number 1810, and by the University of Kuopio
at the farm from mid-February to April and artificial
Animal Ethics Committee. Foxes were of the silver coat
insemination was performed thereafter. Foxes were weighed
phenotype of the red fox born at the farm during the
on digital scales (GWB, Mettler PE 12) at the time of artificial
previous breeding season. One-year-old vixens were
insemination before the animal was returned to its cage. No
selected to ensure uniform breeding success. Each vixen
handling of foxes was permitted after this time to reduce the
was housed in one of two facilities containing 48 steel mesh
possibility of stress-induced abortion (Hartley et al., 1994).
pens (1.1 m ⫻ 1.1 m ⫻ 0.9 m) arranged in two parallel
The weight of each vixen at the time of treatment was
rows with a galvanized steel roof that provided shelter from
extrapolated from a profile of mean weight increases in
rain and snow. Each pen was fitted with insulated wooden
vixens during pregnancy in the previous 2 years that had
breeding boxes with an internal chamber of 0.4 m ⫻ 0.4 m
been kept in the same housing conditions and fed the same
⫻ 0.4 m (Mononen et al., 1995, 1996). Water was provided
diet. This extrapolation resulted in an increase of 8, 10 and
ad libitium via an automatic watering system connected to
15% over the weight recorded at artificial insemination for
the front of each cage. Food was provided each day and
vixens treated at days 28, 35 and 48, respectively.
consisted of a meat slurry that was injected into a feeding
Tablets consisting of 0.5 mg cabergoline and 76 mg
hopper on the front of the cage.
lactose excipient (Dostinex, Pharmacia) were ground to a
fine powder using a mortar and pestle to produce 30 mg
Table 1. Final sample size in each treatment group after removal cabergoline from 60 tablets. Powdered cabergoline was
of red fox (Vulpes vulpes) vixens in which no oestrus or placental apportioned in 25, 50 and 100 µg kg–1 doses for each fox,
scars had been detected or where animals had to be and stored individually in air-tight containers in darkness
killed before whelping at room temperature. A dose of 500 mg lactose was
apportioned for each control fox and stored under the same
Number of animals
treated on each
conditions as those for cabergoline.
Dose of day of pregnancy Foxes were not fed in the 24 h before administration of
cabergoline either cabergoline or the placebo, but water was provided
Group (µg kg–1) n Day 28 Day 35 Day 42 ad libitium. Cabergoline and placebo doses were fed to
foxes in 50 g portions of minced beef. The powdered caber-
1 25 10 3 4 3 goline and placebo were added to the food ration and
50 11 4 4 3 mixed thoroughly. A sheet metal plate (30 cm ⫻ 10 cm)
100 11 4 3 4 was tied using wire to the base of the cage and the mince-
2 50 ⫻ 2 10 4 4 2 beef portion was flattened against the surface of the plate to
3 Placebo ⫻ 2 9 3 3 3
prevent the fox from moving it over the wire floor or into the
breeding box. Before the start of the study, five adult male
Total 51 18 18 15
foxes were fed two doses of 100 µg cabergoline kg–1 at 48 h
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via free accessFertility control in the red fox (Vulpes vulpes) 149
intervals, using the described protocol. Observations of significant differences between the means at P < 0.05.
each male fox revealed that the meat and cabergoline were Mean cub weight per litter and total litter weights for
totally consumed on both occasions and there were no treatment and control groups at weeks 4, 5 and 6 after
detectable losses. No vomiting or adverse effects were whelping were also compared using ANOVA. The growth
observed in the male foxes in the 2 days after ingestion. rate of each cub was calculated by fitting a straight line to
However, ingestion of the meat was confirmed routinely by the cub weights recorded from week 4 to week 8, and rates
observing foxes from a distance of about 5 m and any were then compared using ANOVA.
vomiting observed in a 2 h period thereafter was recorded.
Twelve foxes were allocated randomly to each treatment
Results
group: (i) group 1, a single dose of either 25, 50 and 100 µg
cabergoline kg–1; group 2, a single dose of 50 µg caber- Necropsy and adjusted sample size
goline kg–1, which was repeated 48 h later (2 ⫻ 50 µg kg–1);
No placental scars were detected in seven vixens that
and (iii) group 3, a control group that received a placebo,
did not whelp, although between five and seven corpora
which was repeated 48 h later. Four foxes were selected
lutea were visible in each case. Oestrus was not detected
from each group at day 28, day 35 or day 42 of pregnancy
in one vixen that was to receive a dose of 2 ⫻ 50 µg
and given the appropriate treatment of cabergoline or a
cabergoline kg–1 at day 42, and artificial insemination was
placebo (Table 1). In a separate trial, another ten 1-year-old
not performed. One vixen that was to receive a dose of
vixens were selected from the general farm population, of
25 µg cabergoline kg–1 at day 25 was killed 3 days after
which five vixens received an oral dosage of 100 µg
artificial insemination as a result of a limb injury. These nine
cabergoline kg–1 each day from day 42 to day 46 of preg-
animals were not considered in the assessment of dose–
nancy and the other five vixens received a placebo during
response and the sample size for statistical analysis was
the same period.
adjusted accordingly (Table 1).
Whelping boxes for carbergoline-treated and control foxes
were inspected three times each week, and inspections
Abortion and lactation
commenced 4 weeks after artificial insemination to habituate
the foxes to disturbance. Inspections continued even when an Abortions were not observed in any of the control vixens,
abortion was recorded. The whelping box was inspected for although they were observed in three of four vixens in both
evidence of an abortus, blood, tissues or discharges. Whelping groups that received the 2 ⫻ 50 µg kg–1 and 100 µg kg–1
was detected by direct observation; however, during the doses of cabergoline at day 28 of pregnancy (Table 2).
period between visual inspections, the sound of recently born Emesis was observed in the single vixen treated with 100 µg
cubs was used to determine whether normal lactation and cabergoline kg–1 at day 28 that was not observed to abort
maternal care had started. If abnormal vocalization from cubs and, therefore, it is likely that a full dose of cabergoline was
was recorded, an investigation through direct observation was not ingested. Notably, no abortions were observed at the
carried out the next day. same dose at day 35 and only one occurred in the group
Visual inspections of whelping boxes enabled a record of treated with 100 µg cabergoline kg–1 at day 42 (Table 2).
litter size and cub survival to be maintained. At week 4 after Probit and logistic regression models indicated significant
whelping, cubs were identified individually with subcu- effects (P < 0.05) of dose and timing of cabergoline on the
taneous micro-chip transponders and weighed each week probability of abortion and little difference in the goodness
for 5 weeks. Uterine and ovarian materials were collected of fit for either model. The probability of abortion increased
via ovariohysterectomy between day 73 and day 108 from with dose, but decreased when treatment occurred later in
the day of artificial insemination. The number and presence pregnancy. Lactation commenced in all vixens that
or absence of uterine scars and corpora lutea were whelped and had received a single or double dose of
determined via gross examination (Allen, 1983; Lindstrom, cabergoline, irrespective of cub survival. Copious milk
1986). could be expressed from the teats of all vixens that lost
their litters, although comparative lactation performance
between vixens treated with cabergoline and control
Statistical analysis animals could not be estimated.
Logistic regression and probit analyses were performed Four of five vixens that received 100 µg cabergoline kg–1
to test for significant effects of log (dose) and log (timing) of each day from day 42 to day 46 of pregnancy aborted their
cabergoline administration on abortions (Zar, 1984). The litters, whereas one vixen whelped five cubs that survived to
difference in the median number of cubs born to vixens weaning. One vixen in the control group failed to whelp,
treated with either cabergoline or the placebo from day 42 although no indication of an abortion was detected. Means
to day 46 of pregnancy was tested with the Mann–Whitney of 0.8 (SD = 1.8) and 4.4 (SD = 1.9) cubs per litter were born
rank sum test. One-way ANOVA was performed to in the cabergoline-treated group and the control group,
compare mean litter size at birth with weaning for each respectively. The median number of cubs born per litter for
dose range, and Tukey’s test was performed to test for each group was significantly different (T = 17; P < 0.05).
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via free access150 C. A. Marks et al.
Table 2. Incidence of abortions in red foxes (Vulpes vulpes) in 7
each treatment group
6
Number of cubs
Number of abortions 5
in animals treated on 4
Dose of each day of pregnancy 3
cabergoline 2
Group (µg kg–1) n Day 28 Day 35 Day 42 1
0
1 25 10 1/3 1/4 1/3 Placebo 25 50 2 × 50 100
50 11 1/4 1/4 0/3
Dose (µg cabergoline kg–1)
100 11 3/4 0/3 1/4
2 50 ⫻ 2 10 3/4 0/4 0/2 Fig. 1. Mean number of red fox (Vulpes vulpes) cubs born (䊐) and
3 Placebo ⫻ 2 9 0/3 0/3 0/3 mean number of surviving cubs at weaning ( ) for combined dose
days when vixens received either a dose of the placebo (n = 9), or
Total 51 cabergoline at 25 g kg–1 (n = 7), 50 g kg–1 (n = 9), 2 ⫻ 50 g kg–1
(n = 7) or 100 g kg–1 (n = 7) (P < 0.05).
required (Okkens et al., 1990). The endocrinology of
pregnancy in the red fox is thought to be similar to that of
Litter size, cub survival and growth rates
domestic dogs, although foxes are seasonally mono-oestrus
There was no significant difference in the mean litter and have a gestation period of 52–53 days (Ryan, 1976;
sizes of all vixens at day 2 that had been treated with either Lloyd, 1981; Coman, 1983), compared with an average
a placebo or any dose of cabergoline (F3,27 = 0.979). Cub gestation period of 64 days in domestic dogs (Concannon et
mortality rates in the control group were 6, 7 and 8% for al., 1989). In the red fox, concentrations of progesterone
days 28, 35 and 42, respectively. In the cabergoline-treated peak at the time of implantation and decrease during
groups, litter loss after birth varied between 0 and 100% gestation (Bonnin et al., 1978; Hartley et al., 1994). A
(Table 3). Mean litter survival up to week 4 for all foxes similar profile is observed in the blue fox (Alopex lagopus)
treated with either 25, 50, 2 ⫻ 50 and 100 µg cabergoline (Mondain-Monval et al., 1985) and in dogs (Concannon
kg–1 for combined dose times were significantly different et al., 1989). In hypophysectomized ferrets and dogs, LH
(F4,35 = 3.423; P < 0.05); the group that received 50 µg was not essential for the maintenance of the corpus luteum
cabergoline kg–1 had a lower mean survival rate than (Onclin and Vestegen, 1997). Okkens et al. (1985)
the group that received the placebo (P < 0.05) or 25 µg demonstrated that suppression of LH in dogs did not reduce
cabergoline kg–1 (P < 0.05) (Fig. 1). The value for mean cub progesterone synthesis during the second half of pregnancy
survival for the group that received 2 ⫻ 50 µg cabergoline and concluded that LH was not essential for the
kg–1 was lower than that for the group receiving the morphological or functional integrity of the corpus luteum
placebo, or 25 or 100 µg cabergoline kg–1, although this at this stage. Concomitant administration of prolactin and
difference was not significant (Fig. 1). cabergoline arrested the decrease in progesterone observed
No significant variation in total litter weight was detected in dogs treated with cabergoline alone during the second
in vixens at week 4 (F12,18 = 0.88), week 5 (F12,17 = 0.95) half of pregnancy (Onclin and Verstegen, 1997). A similar
or week 6 (F12,17 = 0.93) after whelping. Similarly, the administration of LH with cabergoline failed to reverse
variation in the mean cub weights for each vixen were not the decrease in progesterone compared with that of dogs
significant at week 4 (F12,18 = 0.31), week 5 (F12,17 = 0.21) that received cabergoline alone. In rats, a decrease in
and week 6 (F12,17 = 0.20) after whelping. There was no prolactin initiated by bromocriptine resulted in the loss of
significant variation in the straight line growth rates, LH receptors, indicating that LH receptors may be
calculated as mean growth rates (g per week), for weeks 4, dependent on prolactin (Grinwich et al., 1976; Murphy and
5, 6, 7 and 8 for each group (F12,17 = 0.19). Rajkumar, 1985; Onclin and Verstegen, 1997). Admini-
stration of exogenous LH in pregnant and non-pregnant
dogs produced only a small and temporary increase in
Discussion
progesterone, and additional doses had a reduced effect
In mammals, the maintenance of pregnancy is dependent (Onclin and Vestegen, 1997). Thus, these studies indicate
on the secretion of luteotrophic hormones from the pituitary that, in dogs, prolactin is likely to be the dominant
and biosynthesis of progesterone by the corpus luteum luteotrophin during the second half of pregnancy. Caber-
(Onclin and Verstegen, 1997). In ruminants, pigs (Sus goline administration resulted in more rapid decreases in
scrofa) and horses (Equus caballus), LH is the primary prolactin at day 30 than at day 25 of pregnancy (Onclin and
luteotrophin; however, in rats (Rattus norvegicus) (Onclin Vestegen, 1997), although administration of cabergoline
and Verstegen, 1997) and ferrets (Mustela putorius) caused abortions in dogs as early as day 25 (Onclin et al.,
(Donovan, 1967; Murphy, 1979), both LH and prolactin are 1993). Progesterone production in dogs was markedly
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via free accessFertility control in the red fox (Vulpes vulpes) 151
reduced by cabergoline administration on day 35 and day Table 3. Cub mortality before weaning in red fox (Vulpes vulpes)
42 of pregnancy, compared with a smaller reduction on day vixens that whelped successfully (n) in each treatment group
28 (Hoffmann et al., 1996). However, the gradual regression
of the corpus luteum in the second half of pregnancy, with a Cub mortality in animals
concomitant decrease in progesterone, occurs despite treated on each day of
pregnancy
increasing availability of prolactin and the maintenance of
Dose of
prolactin receptor concentrations (Fernandes et al., 1987; cabergoline Day 28 Day 35 Day 42
Hoffmann et al., 1996). Dogs hypophysectomized on day 4 Group (µg kg–1) n (%) n (%) n (%)
of pregnancy retained normal concentrations of proges-
terone compared with decreases observed in dogs 1 25 2 (12) 3 (42) 2 (0)
hypophysectomized on day 18 (Okkens et al., 1986; Olson 50 3 (93) 3 (79) 3 (56)
et al., 1989) indicating that, in early pregnancy, the canine 100 1 (0) 3 (12) 3 (13)
corpus luteum may function independently of leutotrophic 2 50 ⫻ 2 1 (100) 4 (28) 2 (29)
support (Okkens et al., 1986, 1990; Fernandes et al., 1987; 3 Placebo ⫻ 2 3 (6) 3 (7) 3 (8)
Post et al., 1988; Vickery et al., 1988; Hoffmann et al.,
Total 10 16 13
1996).
Given the results of the above studies with dogs, in the
present study, it was expected that oral administration of
cabergoline was more likely to induce abortions in foxes at
day 42 than at day 28 of pregnancy. In contrast, cabergoline
doses of 100 µg kg–1 or 2 ⫻ 50 µg kg–1 resulted in abortions Lactation was not terminated in any vixen treated with
at day 28, but were less effective at days 35 and 42. cabergoline at day 28, 35 or 42; however, it was terminated
Although one vixen whelped successfully after receiving in four of five vixens that received 100 µg cabergoline
100 µg cabergoline kg–1, this was probably due to loss of kg–1 each day for 5 days from day 42 of pregnancy. The
cabergoline due to emesis, which was observed after successful whelping and lactation in this vixen may have
treatment. Emesis is a commonly observed side-effect of all been due to a loss of the cabergoline by emesis, although
ergolines used orally at high doses, although the incidence this was not observed during the trial. All five vixens given
is much less with cabergoline (Jöchle et al., 1987, 1989; the placebo whelped normally and lactation was observed
Verstegen, 1993) and emesis was not observed in the in each animal. A pre-partum surge of prolactin is essential
preliminary dosage trial in which two doses of cabergoline for the initiation of lactation (Kann and Denamur, 1974;
of 100 µg kg–1 were used. Nevertheless, Juekenne and Karg and Schams, 1974; Hearne et al., 1998) and for full
Vestegen (1997) observed that a small proportion of dogs development of the mammary glands during pregnancy
receiving high doses of cabergoline were prone to emesis. (Hadley, 1988; Cowie, 1988; Rillema, 1994; Hooghe-Peters
Doses of 100 µg cabergoline kg–1 each day for 5 days and Hooghe, 1995) in a number of eutherian species.
resulted in abortions when administered between day 42 Prolactin-inhibiting drugs, such as bromocriptine, have
and day 47, indicating that prolactin is an essential been demonstrated to inhibit or terminate lactation in
luteotrophin in late pregnancy, but that long-term suppres- domestic dogs (Mayer and Schutze, 1973) and cabergoline
sion is required to induce an abortion, hence the luteolytic administration terminates lactation in cats (Felis domesticus)
effects of cabergoline appear dependent on increased and rats (Jöchle et al., 1989; Ferraro et al., 1995). An oral
duration of administration during the second half of dose of 5 µg per kg per day of cabergoline resulted in
pregnancy in foxes. Luteotrophic factors, possibly of feto– cessation of lactation in beagles at 6 days after whelping,
placental origin, may be important in maintenance of and doses between 2.5 and 5.0 µg per kg per day resulted in
the corpus luteum in late pregnancy in foxes. Placental mammary gland regression. Hearne et al. (1998) observed
luteotrophic hormones are in higher concentrations in rats post-natal mortality in tammar wallabies (Macropus eugenii)
with multiple conceptuses rather than a single conceptus after i.m. doses of cabergoline and bromocriptine, and
(Ochiai et al., 1988; Sugino et al., 1991). Sugino et al. suggested that this mortality was caused by a suppression of
(1994) demonstrated that fetal re-absorption due to restraint the pre-partum pulse of prolactin. It is unlikely that single or
stress, which resulted in decreased serum progesterone double doses of cabergoline administered at days 28, 35
concentrations, was more frequent in rats with fewer con- and 42 inhibited the pre-partum pulse of prolactin, as the
ceptuses and that feto–placental units may influence the half-life of cabergoline is unlikely to suppress prolactin for
maintenance of the corpus luteum. Smith and McDonald more than a few days. Cabergoline remains bound to the D2
(1974) suggested that luteotrophic factors originating pituitary receptors in rats for more than 72 h (Di Salle et al.,
from the placenta may play an important role in the 1983; Onclin and Verstegen, 1997) and the suppression of
maintenance of the corpus luteum in dogs, although such prolactin persists for between 4 and 5 days from a single
activity has not been detected (Talamantes, 1975) and the dose in dogs. In humans, a single oral dose of cabergoline
presence of feto–placental luteotrophic factors has not been causes inhibition of serum prolactin within hours of
investigated in foxes. administration, which lasts for 7 days (Rolland et al., 1991;
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via free access152 C. A. Marks et al.
Ferraro et al., 1995). In the red fox, a single oral dose of another possible means by which cabergoline could affect the
20 µg cabergoline kg–1 resulted in a sustained suppression reproductive success of vixens and this area is also worthy of
of prolactin for at least 3 days (Cowley, 1993). The observed further investigation.
post-natal mortality, which included the partial and full loss
of litters over a 2 week period, is similar to results obtained This study was jointly funded by Environment Australia, the
by Ferraro et al. (1995) in which oral doses of 100–150 µg Phillip Island Nature Park, the Vertebrate Biocontrol Cooperative
cabergoline kg–1 administered once or twice a week Research Centre (VB-CRC) and the Department of Natural
resulted in either the prevention of pregnancy, still birth or Resources and Environment (Victoria). The authors wish to thank
R. Holopainen, A. Helin, M. Tengvall and S. Keski-Nisula from
full or partial post-natal loss of rat pups in the first 12 h after
the Juankoski Fur Farm (Department of Applied Zoology and
parturition. The failure of mammary development in hyp- Veterinary Medicine, University of Kuopio) for their expert
ophysectomized rats injected with exogenous progesterone technical support during this trial. Many thanks to O. Kaasinen for
and oestrogen indicates that pituitary hormones are his willingness to assist with the supply of foxes for the second trial.
essential for mammary development during pregnancy in Staff of the VB-CRC provided useful input during the early design of
this species, although placental lactogens with prolactin- this trial and the authors extend their thanks to B. Seamark, P. Bird
like activity may contribute to mammary development in and L. Hinds. J. Reynolds provided statistical support during the
rats (Daniel and Silberstein, 1987). analysis of data in this study. The manuscript benefited from
An alternative hypothesis to account for the partial loss of constructive criticisms made by M. Renfree, K. Nicholas and two
cubs during the present study is that cabergoline may have anonymous referees.
affected the maternal care of cubs by vixens. In the silver
fox, disorders of maternal care have been related to changes References
in the concentrations of sex steroid hormones and prolactin
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during pregnancy (Oskina, 1991), and litter losses due to of embryos and placental scars Journal of Wildlife Management 47
inadequate maternal behaviour and infanticide by prim- 860–863
iparous silver foxes have also been well documented Anon (1996) Threat Abatement Plan for Predation of Wildlife by the
(Braastad and Bakken, 1993). In the present study, the effect European Red Fox Australian Nature Conservation Agency, Canberra
Belcher CA (1998) Susceptibility of the tiger quoll, Dasyurus maculatus, and
of cabergoline on maternal behaviour and the contribution
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