Coat colour changes associated with cabergoline administration in bitches.

Cabergoline or bromocriptine were administered orally to 60 bitches at doses of 5 microg/kg and 15 microg/kg daily, respectively, for two to 45 days for the treatment of pseudopregnancy or for oestrus induction. Seven of the dogs which received cabergoline for more than 14 days developed coat colour changes from the second week of administration to the next coat shedding. Of these, fawn-coloured bitches developed a yellowish coat colour while Argentine boar hounds became black spotted, mainly on their extremities. In previous untreated oestrous periods, these bitches had shown no coat colour changes. It is concluded that a colour shift in certain haircoats of particular breeds could be mediated through the inhibition of the secretion of melanocyte-stimulating hormone by the administration of the dopaminergic agonist cabergoline for more than two weeks. Transient coat colour changes should be considered a possible side effect when planning long-term treatment with dopaminergic agonists in dogs.

Study of the change of prolactin and progesterone during dopaminergic agonist treatments in pseudopregnant bitches.

In order to clarify the role of prolactin (PRL) and progesterone (P(4)) in the pathophysiology of canine pseudopregnancy (PSP) we designed an experiment, where we induced an abrupt pharmacological blockade of PRL secretion with dopaminergic agonists (DA) or placebo (PL). Thirty overtly pseudopregnant (PSPT) bitches were randomly allocated to three groups of 10 animals each: PL, bromocriptine (BR), and cabergoline (CA), which were treated with PL, 7.5microg/kg BR and 5microg/kg CA, respectively. On days 1, 7 and 14 (day 0: beginning of the treatment) all the animals were classified into grades of intensity of PSP clinical signs, considering serum or milk secretion and enlargement of the mammary glands. Presence or absence of treatment side effects were recorded and blood samples for PRL and P(4) determinations collected. Serum PRL and P(4) concentrations (ng/ml) of all the animals on day 1 were (least squares means [LSM]+/-S.E.M.) 17.70+/-2.05 and 1.13+/-0.13, respectively. During the experiment, serum PRL and P(4) concentrations decreased (day effect, P<0.05). During the experiment, serum PRL concentrations were lower in the DA treated group (BR and CA) compared with PL group (P<0.05). After a week of treatment, the percentage change of PRL was -62.52 versus 102.16+/-46.20 (P<0.01) for the treated (BR and CA) and PL groups, respectively. Conversely, no significant differences were found in the percent change in PRL between the BR and the CA groups nor in P(4) percentage change among all groups for the same week. Significant differences in the achievement of complete remission between treated and PL groups were found on days 7 (40 versus 0%, P<0.05) and 14 (90 versus 0%, P<0.01). No significant correlation between PRL and P(4) was found on day 1 in any of the animals. However, a significant correlation for the same hormones was found on days 7 and 14 for the DA treated groups (r=0.46, P<0.01). While in the PL group, PRL concentrations and intensity of clinical signs were not significantly correlated on days 1, 7 and 14; in the DA treated groups they were significantly correlated on days 7 and 14 (r=0.34, P<0.05). The presence of a positive correlation between PRL concentrations and the grades of intensity of clinical signs in the treated animals indicates the major role of PRL in PSP physiopathology. However, the lack of correlation during spontaneous involution of PSP in the PL group demonstrates that PRL concentrations do not completely explain the problem. In summary, abrupt changes in serum PRL seemed to be more important in ceasing PSP signs than total PRL concentrations in these groups of animals.

Delusional pregnancy in a patient with primary sterility.

The case of a patient suffering from primary sterility who developed a well-systemized delusion of pregnancy is described. The patient did not have a history of psychiatric disorder or organic cerebral pathology. No history of epilepsy was detected in this patient contrary to the reports in the literature, and these facts have pathogenic relevance in delusional pregnancy. The importance of psychological factors in the development of a delusion of pregnancy is discussed.

[Plasma prolactin concentration and the effect of metergoline in pseudopregnant Afghan hounds]. / Plasma-prolactineconcentraties en het effect van metergoline bij pseudogravide Afghaanse windhonden.

The effects of metergoline, a 5-hydroxytryptamine (serotinin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-psueodopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentration of prolactine in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

A study of the aetiology of pseudopregnancy in the bitch and the effect of cabergoline therapy.

Thirty-two permanently pseudopregnant bitches were treated with the anti-prolactin drug cabergoline. They had all been ovariohysterectomised up to five months after their last season, in some cases over two years previously, when most were reported as showing no signs of the condition. The clinical signs were mainly behavioural, the majority being aggressive, and a small number were lactating. The efficiency of the cabergoline therapy was classified by the owners as 'excellent' or 'good' in 50 per cent of the cases, and fair in 36 per cent. The rate of success was markedly better than in similar cases treated with reproductive steroids. In all but one of the bitches, the plasma prolactin concentrations were basal.

Changes in refractoriness of rabbit corpora lutea to a prostaglandin F2 alpha analogue, alfaprostol, during pseudopregnancy.

The responsiveness of rabbit corpus luteum to 200 micrograms of the prostaglandin F2 alpha (PGF2 alpha) analogue, alfaprostol, between Days 3 and 9 of pseudopregnancy was assessed by evaluating the decline in plasma progesterone after treatment with PGF2 alpha in 81 New Zealand White (NZW) rabbits. On Days 3-5, functional luteolysis was not observed. On Days 6, 7, and 8 of pseudopregnancy, the number of rabbits responsive to PGF2 alpha, rose from 38% to 71% and 83%, respectively. In the other cases, the effect of the PGF2 alpha analogue was transient as CL recovered in the following 2 or 3 days. By contrast, on Day 9 luteolysis was effective and persistent in all the animals. In rabbits treated on Day 9, progesterone decreased gradually from 10.6 +/- 0.7 within the first 6 h, but fell to 3.6 +/- 1.5 ng/mL (p < 0.01) 12 h after PGF2 alpha and to 0.2 +/- 0.1 ng/mL (p < 0.01) 24 h later.

Effect and mechanisms of the anti-prolactin drug cabergoline on pseudopregnancy in the bitch.

A potent anti-prolactin drug, cabergoline, administered orally for five days, was clinically successful in treating three different clinical manifestations of pseudopregnancy in referred bitches. The clinical conditions treated were categorised as standard pseudopregnant bitches (n = 8), those previously unsuccessfully treated with hormones (n = 10) and those which had behavioural pseudopregnancy following ovariohysterectomy (n = 8). The number of bitches whose owners reported a 'good' response was seven out of eight, six out of 10 and six out of eight, respectively. There were very few side effects in that only one bitch vomited following treatment. The clinical response did not necessarily appear to be related to an alteration in circulating prolactin concentrations, suggesting that the drug may have a direct effect on the tissues as well as in most cases reducing the plasma prolactin concentrations.

Plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and the effect of metergoline.

The effect of metergoline, a 5-hydroxytryptamine (serotonin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-pseudopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentrations of prolactin in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

[The treatment of pseudopregnancy in the bitch with prolactin inhibitors metergoline and bromocriptine]. / Untersuchung zur Behandlung der Scheinträchtigkeit der Hündin mit den Prolaktinhemmern Metergolin und Bromocryptin.

In the present study, the prolactin inhibitor Metergoline was compared with Bromocriptine and tested against a placebo in 63 pseudogravid bitches. Bromocriptine has already been tested successfully in numerous investigations on the therapy of canine pseudogravidity, but--probably because of its high price and vomitus as a frequent side effect--it has not been really introduced as a therapeutical device in canine practice. It can be deduced from the results presented herein that prolactin is essential for maintaining the pseudogravidity, but keeping up the lactation process--especially galactopoiesis--can probably not be ascribed solely to prolactin. However, prolactin definitely plays an essential role in the hormonal scenario, the detailed regulating mechanisms of which are not known until today. Thus, no statistically convincing therapy outcome could be achieved by the prolactin inhibitors compared to the placebo group. A tendency towards earlier regression of the symptoms "mammogenesis", "behavioural change" and "galactorrhea" was however present in the treated animals. A striking difference was the much more lively behaviour of the bitches with 53% being more lively in the Metergoline group, 37% in the Bromocriptine and 10% in the placebo group. There were also clear differences in the compatibility of the drugs; in the Bromocriptine group, 30% of the animals vomited, in the Metergoline only 6.3%. This however did not lead to termination of the therapy in any case. In two cases of the Metergoline group (6.3%), the medication was ended due to extreme restlessness.

Hydrometra in dairy goats: reproductive performance after treatment with prostaglandins.

An intramuscular injection of 5 mg dinoprost caused a discharge of uterine fluid (cloudburst) in 49 cases of hydrometra in goats during the breeding seasons of 1988, 1989 and 1990. A spontaneous oestrus after the cloudburst was allowed to occur in 20 of the goats; in nine (45 per cent) of them a hydrometra recurred, three conceived at the first oestrus and eight returned to oestrus. Oestrus was induced in 29 other cases by means of a second intramuscular administration of 5 mg dinoprost, 12 days after the cloudburst. In this group a hydrometra recurred in only one goat, 14 goats (48 per cent) conceived at the first oestrus and 14 returned to oestrus. Of the animals in which a pseudopregnancy occurred once or more during the same breeding season, 85 per cent became pregnant, compared with 97 per cent of unaffected older goats. The mean number of kids of the goats that became pregnant and kidded after treatment for hydrometra was 2.0 compared with 2.3 for unaffected animals. The results indicate that a single administration of prostaglandin is not a satisfactory therapy for a hydrometra, but that reproductive performance improves when a second injection is given 12 days after the cloudburst.

Diethylstilboestrol--clinical pharmacology and alternatives in small animal practice.

Diethylstilboestrol is currently only available in Australia for oral use in dogs and cats. As an orally and systemically active non-steroidal oestrogen, DES has been widely used in small animal veterinary medicine for a variety of indications. A review of the literature reveals that many of the recommendations for use are founded on anecdotal or unreported clinical observations. While many of the uses may be valid, accurate determinations of optimum dosing regimens have not been defined. This is especially unfortunate in view of the potential toxicity of DES to small animals. Nevertheless, particularly in cases of low-dose intermittent administration, oral DES appears indicated at least until data on alternative safe and effective interventions become available.

Is the antiprogestin RU486 luteolytic in rats?

Subcutaneous injections of RU486 on Day 1, Day 4 or Days 3 and 4 of pregnancy in rats induced abortion of the embryo and transient vaginal cornification. Nevertheless, most corpora lutea appeared to be functional at autopsy on Day 12. The same treatments in pseudopregnant rats also produced transient vaginal cornification, but did not terminate pseudopregnancy. This suggests that transient antagonism of progesterone by RU486 does not terminate function of the corpus luteum in rats and that positive feedback by progesterone is not essential for continuing luteal function in rats.

The direct luteotropic effect of tokishakuyakusan in rats.

The effect of Tokishakuyakusan (TS) on the corpus luteum function in pseudopregnant rats was examined in vivo. On day 4 of pseudopregnancy (PSP), induced by cervical stimulation, TS (20 micrograms) stimulated the progesterone secretion rate (PSR) in the ovarian venous plasma. There was also a significant increase in the rate of progesterone to 20 alpha-OH-progesterone. However, on day 8 of PSP, there was no apparent change in PSR in the ovarian venous plasma after the administration of TS. These data suggest that the sensitivity to TS of the corpus luteum varies according to its age.

Pseudocyesis and depression. Etiological and treatment considerations.

Pseudocysesis, or false pregnancy, is generally classified as a conversion symptom and is usually treated as such with little success. Depression, however, is a commonly associated phenomenon and is typically neglected in the formulation and treatment of this disorder. This report presents a case study in which the patient was referred for evaluation of pseudocyetic symptoms, but depression was judged to be the underlying problem. Antidepressant therapy was instituted and found to be effective in ameliorating the pseudocyetic symptoms. Treatment implications of pseudocyesis as an artifact or concomitant of depression are discussed.

Treatment of pseudopregnancy with bromocriptin, an ergot alkaloid.

One hundred and forty-two dogs with single or multiple pseudopregnancies were treated with bromocriptin at three different dose rates and once in combination with mobilerone. The treatments that scored best were 30 micrograms/kg bromocriptin for 16 days and 10 micrograms/kg bromocriptin for 10 days. Vomiting was a frequent side effect (about 20 per cent of cases) and was treated successfully with metoclopramide at a dosage of 0.5 mg/kg. Metoclopramide had no effect on the effectiveness of the bromocriptin.

Efficacy and dosage titration study of mibolerone for treatment of pseudopregnancy in the bitch.

A controlled, blind-labeled, dose-response field trial was conducted to evaluate the efficacy of mibolerone as a treatment for pseudopregnancy in the bitch. Bitches were treated orally for 5 consecutive days with one of the following dosages of mibolerone: 0.008, 0.016, or 0.025 mg/kg of body weight. Changes in psychologic signs (nesting behavior, mothering inanimate objects, and self-nursing) or physical signs (mammary gland enlargement and secretion of a liquid or milk, ie, galactorrhea) were noted. The period within which the improvement occurred also was noted. There were 63 cases distributed over the 3 dosages--19 at 0.008 mg/kg, 22 at 0.016 mg/kg, and 22 at 0.025 mg/kg. Seventeen bitches given a placebo served as controls. There were significant differences in improvement of clinical signs among the dosages for the combinations of psychologic (P less than 0.001), physical (P less than 0.01), psychologic or physical (P less than 0.001), and psychologic and physical (P less than 0.001). The projected optimal dosages were: 0.016 mg/kg, 0.013 mg/kg, 0.014 mg/kg, and 0.015 mg/kg for the psychologic, physical, psychologic or physical, and psychologic and physical signs, respectively. Of the 3 dosages used, 0.016 mg/kg (for 5 consecutive days) was estimated to be optimal for improvement of the physiologic signs of pseudopregnancy.