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PubMed2001

Contribution of angiotensin II, endothelin 1 and the endothelium to the slow inotropic response to stretch in ferret papillary muscle.

We investigated the contribution of angiotensin II and endothelin I to the slow positive inotropic response observed following stretch of isolated ferret papillary muscle from 88% to 98% of the length at which maximum force is generated. Angiotensin antagonists losartan and saralasin did not affect the magnitude of the slow response in ferret papillary muscle. The ETA-selective antagonist BQ123 slightly reduced the magnitude of the slow response (P > 0.05). In the presence of PD145065 (an ETA and ETB antagonist), the magnitude of the slow response was reduced significantly by 50%. Removal of the endothelium with 1% Triton X-100 reversed the slow response to stretch. We conclude that, in the ferret, endothelin I acting through ETA and ETB receptors, contributes to the slow response although it is not the sole mediator. Angiotensin II is not a prerequisite for the slow response to stretch. We have shown for the first time that the endocardial endothelium plays a pivotal role in this phenomenon in cardiac papillary muscle.

Angiotensin II↗

PubMed1985

In vitro metabolism of [3H]-peptide leukotrienes in human and ferret lung: a comparison with the guinea pig.

Fragmented lung tissue prepared from human, ferret and guinea pig converted [3H]-leukotriene C4 ([3H]-LTC4) to [3H]-LTD4 and [3H]-LTE4. [3H]-LTD4 was the major product recovered from incubations with human and guinea pig lung, whereas [3H]-LTE4 was the predominant metabolite in ferret. Kinetic analysis in human lung yielded a much faster rate for the conversion of [3H]-LTC4 to [3H]-LTD4+E4 than for the conversion of [3H]-LTD4 to [3H]-LTE4. In all three species serine-borate complex blocked the metabolism of [3H]-LTC4, whereas L-cysteine blocked the metabolism of [3H]-LTD4. These studies demonstrate that guinea-pig and human lungs have a similar metabolic pattern and capacity which is dissimilar to the ferret.

Animals↗

PubMed1983

Some acoustic properties of neurones in the ferret inferior colliculus.

Single neurones in the central nucleus of the ferret inferior colliculus (ICC) were studied using extracellular recording. Responses to pure tone stimuli were analyzed to assess the frequency organization of the nucleus, the sensitivity and tuning properties of neurones and the effects of binaural sound presentation. Excitatory tuning curves had the characteristic shape found for neurones in the auditory systems of other species. Many ferret neurones were inhibited by stimulus frequencies on either side of the range producing excitatory responses. Sharpness of excitatory tuning was found to be comparable with that reported for the cat. Neurones having best frequencies in the range 4-15 kHz showed the greatest sensitivity. All electrode penetrations revealed a dorsal-to-ventral progression of neurones of increasing best frequency. Some neurones were classified according to the predominant type of input from each ear. Over 80% of these units were binaurally influenced. Nearly all cells received an excitatory input from the contralateral ear and about one-third of those units were excited by ipsilateral stimulation. The remainder showed either a simple inhibitory ipsilateral input or ipsilateral inhibition that was manifested as a suppression of the excitatory, contralateral response. These experiments demonstrate that the ferret may be a satisfactory alternative to other carnivores for studies of the auditory system.

Animals↗

PubMed1985

Distribution of ganglion cells in the retina of adult pigmented ferret.

The retinal ganglion cell distribution in adult pigmented ferret was mapped in Nissl-stained retinas and in retinas back-filled with HRP after large bilateral injections of the enzyme into the brain. In common with other carnivores the ferret has an area of peak cell density equivalent to the area centralis and a prominent visual streak of high cell density extending horizontally across the retina. The maximum ganglion cell densities for the retinas were estimated to be 3500-5200 cells/mm2 in Nissl-stained, dehydrated retinas and 3300-4300 cells/mm2 in HRP-labelled, undehydrated retinas. Three cell types were distinguished in the HRP-labelled retinas and they appear to correspond to alpha-, beta- and gamma-cell types of cat retina. However, unlike in cat, the retinal ganglion cells of the ferret do not consistently fall into 3 distinct groups with respect to cell size, nor is there a tendency for the cells in the area centralis to be smaller than those in the peripheral retina. Estimates for the total number of ganglion cells of 82,000 and 88,000 were obtained from Nissl-stained retinas, and of 74,000, 75,000 and 78,000 from HRP-labelled retinas.

Animals↗

PubMed1986

Sexual dimorphism in the preoptic/anterior hypothalamic area of ferrets: effects of adult exposure to sex steroids.

The organization of neuronal cell bodies in the caudal preoptic area (POA) and rostral anterior hypothalamic area (AH) was studied in Nissl-stained brain sections from adult male and female ferrets. Computer-assisted image-analysis procedures were developed to help estimate the areas of cellular density and the sizes of individual perikarya. At the junction of the POA and AH, a bilateral dorsal-medial group of neurons was apparent only in male ferrets (dorsal nucleus). At the same coronal level, a ventral-medial group of neurons was apparent bilaterally in both males and females (ventral nucleus). The mean somal area of cells in the dorsal nucleus of males was significantly greater than the mean somal area of cells in the corresponding dorsal region of females or in the ventral nucleus of both sexes. The dorsal nucleus was clearly discernible in adult males regardless of their hormonal status, although cells in the dorsal nucleus were larger in intact breeding males or gonadectomized males given testosterone, estradiol or dihydrotestosterone than in gonadectomized males given no gonadal hormones or given progesterone. Neither the grouping of large cells nor the steroid-induced increase in cell size, characteristic of the male dorsal nucleus, was seen in the comparable dorsal region of females. The sex difference in cellular organization observed in the ferret at the junction of the POA and AH is the first difference of this type to be seen in the POA/AH of a non-rodent mammalian species. Its identification will, hopefully, aid in the analysis of the neural mechanisms that control various sex-specific behaviors in this species.

Animals↗

PubMed1988

Primary auditory cortex in the ferret (Mustela putorius): neural response properties and topographic organization.

Microelectrode recording studies were made of the crown of the ectosylvian auditory cortex of barbiturate-anesthetized ferrets, using calibrated, sealed acoustic stimulus delivery systems. We confirmed our previous finding using free-field stimuli that this region of the ferret's cerebral cortex contains a tonotopically organized field in which neurons are briskly excited by the onset of tonal stimuli. The vast majority of neurons in this field were narrowly tuned to tone pulse frequency, with Q factors comparable to those described for cortical cells in other species. The distribution of minimum tone thresholds across the frequency representation of this field paralleled the behavioral audiogram in the same species. The majority of neurons received input from both ears, and the natures of the influences exerted by tonal stimuli at the two ears were similar in form to those described for other carnivores. The various binaural cell types had characteristic frequencies that spanned the entire tonal spectrum represented in the cortex. Preliminary mapping studies revealed that there may be a topographic segregation of cells according to their binaural interactions. The basic properties of cells in this region of the ferret's cerebrum are similar to those previously described for the cat's primary auditory cortex. The data on the binaural properties of these cells, and the spatial distribution of those cells, provide the first evidence in a species other than the cat for segregated binaural representation in the auditory cortex.

Acoustic Stimulation↗

PubMed1990

Effects of lesions of a sexually dimorphic nucleus in the preoptic/anterior hypothalamic area on the expression of androgen- and estrogen-dependent sexual behaviors in male ferrets.

The male nucleus of the preoptic/anterior hypothalamic area (MN-POA/AH) is a sexually dimorphic structure present in male, but not in female ferrets. Ovariectomized female ferrets given increasing dosages of estradiol benzoate (EB) normally run faster towards a stud male in an L-maze (i.e. become more proceptive). In two separate experiments, only gonadectomized males with bilateral damage to the MN-POA/AH following large or small electrolytic lesions approached stud males more quickly in response to EB. By contrast, males which received sham lesions, unilateral large POA/AH lesions, or bilateral lesions which missed the MN-POA/AH on at least one side failed to show EB-induced reductions in approach latencies in pre- or post-operative tests. Males with large POA/AH lesions also displayed significant post-operative decrements in masculine sexual behaviors during treatment with a high dose of testosterone propionate (TP). Less severe, but statistically significant deficits in masculine coital performance were also observed in males with small lesions which damaged the MN-POA/AH bilaterally; however, the ability of these males to achieve intromissions appeared normal. Together, these results suggest that the MN-POA/AH of the male ferret exerts an inhibitory influence on estrogen-dependent proceptive responsiveness, but play only a minor role in the control of masculine coital behavior.

Animals↗

PubMed1990

Medullary sites mediating some abdominal vagal reflexes in the ferret using [14C]2-deoxyglucose.

The central projections of some abdominal visceral afferents passing through the vagal communicating branch were studied in anesthetized ferrets using [14C]2-deoxyglucose autoradiography. The reflex effects of electrical stimulation of the vagal communicating branch were studied while measurements of jejunal motor activity and transmural potential difference, a marker of electrogenic epithelial transport were made concurrently. The aim of this study was to examine brainstem projections of some afferent fibers in the communicating branch of the thoracic vagus nerve that are necessary for the reflex regulation of small intestinal motor activity and epithelial transport. In urethane-anesthetized ferrets, electrical stimulation of the cut central end of the vagal communicating branch increased jejunal motor activity and electrogenic epithelial transport. In addition, glucose utilization in the left medial sub-nucleus of the nucleus tractus solitarius and the dorsal motor nucleus of the vagus was significantly increased as compared with sham-operated non-stimulated control animals. Identical areas on the contralateral side of the brain showed no change in glucose utilization as compared with sham-operated non-stimulated controls. This functional brain-mapping study strongly suggests that the left medial sub-nucleus of the nucleus tractus solitarius and the dorsal motor nucleus of the vagus, in the ferret, are involved in processing alimentary afferent activity from both the small intestinal musculature and epithelium as well as the reflex changes in efferent vagal nerve activity to the same regions of the alimentary tract.

Afferent Pathways↗

PubMed1996

Involvement of dopamine D3 receptors in the area postrema in R(+)-7-OH-DPAT-induced emesis in the ferret.

We investigated the possible involvement of dopamine D3 receptors in R(+)-7-hydroxy-2-(N,N-di-n-propylamino)tetraline (R(+)-7-OH-DPAT)-induced emesis in the ferret. The R(+)enantiomer of 7-OH-DPAT (0.03-1 mg/kg, s.c.) caused emesis in a dose-dependent manner, whereas the S(-)enantiomer, even at 1 mg/kg s.c. failed to induce emesis. Quinpirole (0.1-1.0 mg/kg) and apomorphine (0.3 mg/kg, s.c. only) also elicited an emetic response. S(-)-Eticlopride, which has a high affinity for the dopamine D3 receptor, antagonized R(+)-7-OH-DPAT (0.3 mg/kg, s.c.)-induced emesis (ID50 1.4 micrograms/kg, s.c.). R(+)-7-OH-DPAT (0.1-1.0 microgram) administered into the 4th cerebral ventricle dose dependently induced emesis within 1 min of dosing in ferrets. Intracerebroventricularly administered S(-)-eticlopride (0.01-1 microgram) also inhibited the emesis induced by s.c. administration of R(+)-7-OH-DPAT. The emetic effect of R(+)-7-OH-DPAT was unaffected by abdominal vagotomy but was markedly reduced by ablation of the area postrema. These results suggest that dopamine D3 receptors in the area postrema play an important role in R(+)-7-OH-DPAT-induced emesis in the ferret.

Animals↗

PubMed1984

Tapetum lucidum in the pigmented and albino ferret.

Light and electron microscopy showed that the tapetum lucidum in the pigmented ferret is morphologically indistinguishable from that in the albino ferret. The matrix of the rods of the tapetal cells was strongly osmiophilic, but glutaraldehyde fixation before osmium tetroxide treatment caused a dissolution of the matrix material. It has been proposed that the tapetal cells are modified melanocytes and that the tapetal rods are composed of melanin, but it can be concluded from our data that the matrix of the tapetal rods is not melanin. Further studies by plasma-atomic emission spectrometry showed that the tapetal cells are very rich in zinc, with similar levels in pigmented and albino ferrets. Excessive concentrations of other metals were not observed. Histochemical demonstration of heavy metal showed that the zinc is present in the tapetal rods and indicated a localization mainly in the rod membranes.

Albinism↗

PubMed1987

In vitro binding and utilization of lipoproteins by luteal cells from ferrets treated with dopaminergic drugs during pseudopregnancy.

The effects of administration of dopaminergic drugs in vivo on the binding and utilization of lipoproteins for progesterone synthesis in vitro by ferret luteal cells were investigated. Pimozide, a dopamine antagonist, and bromoergocriptine (CB-154), a dopamine agonist, were administered to pseudopregnant ferrets to alter prolactin (PRL) concentrations daily beginning the day after ovulation. The control group received the vehicle solution only. Corpora lutea taken on Day 13 after ovulation were dissociated and the cells were incubated with canine lipoproteins, cyclic adenosine monophosphate (cAMP), and 5-cholesten-3 beta-25-diol (25-OH-cholesterol). Canine high-density lipoprotein (HDL) and low-density lipoprotein (LDL) stimulated progesterone accumulation by luteal cells from pimozide-treated animals but not from CB-154-treated ferrets. However, when 25-OH-cholesterol, which bypasses the LDL receptor, was provided as the substrate, steroidogenesis was stimulated in all groups. Together these observations suggest that dopaminergic alteration of PRL levels preferentially affects the utilization of lipoproteins. The uptake of canine HDL and LDL by luteal cells was saturable, and a high degree of cross-reactivity was observed. Heparin released surface-bound HDL and LDL, suggesting that HDL was binding to the LDL receptor. The quantity of LDL which could be released from luteal cells by heparin treatment was greater in animals treated with pimozide and decreased by treatment with CB-154, relative to luteal cells from control animals. It was concluded that the chronic administration of pimozide or CB-154 alters serum PRL levels in vivo, and influences the subsequent binding and utilization of lipoproteins by luteal cells in vitro. PRL may increase the number of LDL binding sites in luteal cells, thereby enhancing lipoprotein uptake for progesterone synthesis.

Animals↗

PubMed1987

Role for prenatal estrogen in the development of masculine sexual behavior in the male ferret.

Previous studies have shown that neonatal exposure to testosterone is essential for coital masculinization in male ferrets. In the present experiments, masculine sexual behavior was diminished in male ferrets by prenatal exposure to drugs which inhibited estrogenic stimulation of the brain. Similarly timed prenatal treatments with testosterone failed to masculinize the behavior of female offspring. We hypothesize that prenatal exposure of the male ferret to estrogen, derived from the neural aromatization of circulating androgen, may sensitize the developing brain to the subsequent masculinizing action of testosterone shortly after birth.

Androstatrienes↗

PubMed1990

Endocrine correlates of mating-induced reductions in estrous behaviour in an induced ovulator, the ferret.

Experiments were conducted to assess the time course of behavioral and endocrine changes which occur in female ferrets as they switch from estrus to the pseudopregnant state. Significant reductions in females' acceptance of neck gripping by a stimulus male (receptivity) and in their latency to approach a stimulus male in an L-maze (proceptivity) were first observed 3 days after receipt of an intromission; no such changes occurred in other females which were only neck gripped by stimulus males during the initial test session. Corpora lutea were later found only in the ovaries of females which received intromissions, confirming that ovulation had occurred in these animals. Plasma concentrations of prostaglandin E1, prostaglandin F2 alpha, and the 13,14-dihydro 15-keto metabolite of prostaglandin F2 alpha (PGFM) were unchanged in female ferrets for 4-5 days after receipt of an intromission. By contrast, plasma concentrations of progesterone were significantly elevated beginning 5 days after, whereas plasma estradiol was significantly reduced beginning 4 days after receipt of an intromission. Daily sc administration of the progesterone receptor antagonist. RU 38486, significantly retarded the lengthening in females' approach latencies to a stimulus male, suggesting that postcoital elevations in circulating progesterone normally contribute to the expected decline in proceptive responsiveness. By contrast, postcoital reductions in acceptance quotients occurred at equivalent rates in females treated with RU 38486 versus vehicle, leading us to infer that postcoital reductions in estrogenic stimulation may cause this decline in ferrets' receptive responsiveness.

Animals↗

PubMed1991

Reciprocal relationships between pulsatile androgen secretion and the expression of mating behavior in adult male ferrets.

The pulsatile secretion of androgen was similar over a 12-hr period in breeding male ferrets implanted with jugular catheters which either achieved an intromission with an estrous female or received no socio-sexual contact. This negative result contrasts with the previous demonstration (Carroll, Erskine, and Baum, 1987, Endocrinology 121, 1349-1359) of a significant, delayed rise in mean plasma androgen concentrations in breeding male ferrets 5-12 hr after mating. Males used in that previous study had lower initial mean plasma levels of androgen and smaller testis diameters than the present males. We therefore asked whether differences in circulating androgen levels, characteristic of males in different phases of the seasonal breeding cycle, might affect the expression of mating behavior. Castrated males given 0, 0.2, 2.0, or 5.0 mg/kg of testosterone propionate (TP) showed dose-related increases in the expression of different components of sexual behavior, including neck gripping, mounting, and intromitting. Surprisingly, intromissive performance was significantly better in intact breeding males than in castrates given even the highest dosage of TP. These results suggest that ferrets' mating performance may vary with seasonal variations in androgen availability, and that the ability of males to exhibit a postcoital increase in the testicular secretion of androgen may be limited to the beginning or end of the breeding season, when circulating levels of androgen are relatively low. Mating-induced increments in androgen secretion at these times may enhance subsequent reproductive success by facilitating males' intromissive capacity, which is required for the induction of ovulation and optimal sperm transport in female partners.

Animals↗

PubMed1987

Emesis induced by cisplatin in the ferret as a model for the detection of anti-emetic drugs.

The intravenous injection of cisplatin in the ferret caused a consistent emetic (vomiting/retching) response. Emesis induced by cisplatin was abolished by the 5-hydroxytryptamine (5-HT) M-receptor antagonists ICS205-930, zacopride, dazopride and metoclopramide. The neuroleptic agents haloperidol, fluphenazine, domperidone, sulpiride and tiapride also antagonized emesis induced by cisplatin but only a proportion of the animals were completely protected and diazepam and prednisolone only reduced the intensity of the response. It is concluded that compounds used in the clinic to antagonise emesis induced by chemotherapy are effective in the ferret model. Antagonism of emesis induced by cisplatin in the ferret was most potently achieved by the use of the 5-HT M-receptor antagonists ICS205-930 and zacopride. However, an antagonism of dopamine receptors would appear relevant to the anti-emetic effects of the neuroleptic agents and may contribute to the anti-emetic effects of metoclopramide. Diazepam and prednisolone exert their modest antagonism by unknown mechanisms. The use of the 5-HT M-receptor antagonists is revealed as a novel approach to the treatment of emesis induced by cisplatin.

Animals↗

PubMed1986

Annual rhythm and hormonal control of predatory behavior in female ferrets.

The predatory behavior of female ferrets shows seasonal fluctuations which appear to be affected by estradiol. Under natural lighting conditions in the laboratory the annual rhythm of the behavior was observed during anestrus, estrus, pregnancy, pseudopregnancy and lactating period. Females in heat failed to show predatory behavior whereas females in anestrus killed their prey. Exposure of anestrous ferrets to a prolonged illumination (LD 16:8) during winter induced an estrus which inhibited predatory behavior. When estrus was terminated with human chorionic gonadotropin (HCG), predatory behavior did not further regress as it did in control runs. Thus, during the period of estrus, when estrogen levels are presumably high, predatory behavior was inhibited. To prove a possible interdependency of estrogen and predatory behavior, estradiol-17 beta-valerat was chronically administered. This treatment induced the estrous cycle one day after the first injection. Inhibition of predatory behavior occurred following a delay of 28 days. Thus, fluctuations of estradiol levels are a factor which may affect fluctuations of predatory behavior in female ferrets.

Animals↗

PubMed1986

Effect of prenatal exposure to aromatase inhibitor, testosterone, or antiandrogen on the development of feminine sexual behavior in ferrets of both sexes.

Experiments were conducted to assess the role of prenatal exposure of the brain to estrogen in controlling the development of proceptive and receptive feminine sexual behavior in ferrets of both sexes. Female ferrets, deprived prenatally of estrogen via maternal ovariectomy on gestational day 30 (42-day gestation) plus SC implantation of an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), into their mothers, were significantly less receptive than control females when tested in adulthood after ovariectomy and administration of low (5 and 10 micrograms/kg) dosages of estradiol benzoate (EB). However, they were no less receptive than control females in response to a high (15 micrograms/kg) dosage of EB. Estrogen-deprived females showed EB-induced reductions in approach latencies to a stud male (proceptive responses) which were equivalent to those of control females. These results suggest that estrogenic stimulation of the female brain during fetal development enhances later receptive responsiveness to estradiol. However, prenatal estrogen appears not to be an absolute requirement for the development of receptive or proceptive coital capacity in females. In a previous study castrated male ferrets failed to show EB-induced reductions in the latency to approach a sexually active male, indicating that they were proceptively defeminized. In the present study females exposed prenatally to exogenous testosterone also failed to display significant EB-induced reductions in approach latencies to a sexually active male. Males deprived prenatally of estrogen ran faster to a stud male after adult administration of increasing dosages of EB.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstatrienes↗

PubMed1992

Sexual dimorphism in the effects of mating on the in vitro release of LHRH from the ferret mediobasal hypothalamus.

A sexually dimorphic pattern in the secretion of luteinizing hormone (LH) has previously been shown to occur in response to mating in an induced ovulating species, the ferret, with mating augmenting the secretion of LH in females but not in males. The aim of this study was to determine whether this dimorphic pattern in the postcoital secretion of LH reflects a dimorphic effect of mating on the neural release of luteinizing hormone releasing hormone (LHRH). The effect of mating on the in vitro release of LHRH from mediobasal hypothalami (MBH) collected from breeding male and female ferrets was studied. Luteinizing hormone releasing hormone release and content were significantly reduced in tissues from estrous females sacrificed 0.25 h after mating compared to unpaired estrous females and estrous females sacrificed 1 or 2.6 h after the mating stimulus. By contrast, the release of LHRH from MBH fragments and LHRH tissue content were equivalent in breeding males that were sacrificed 0.25 h after mating and in breeding males that were left unpaired. These data suggest that the postcoital surge of LH in the female ferret is preceded by a release of LHRH that initially depletes neuronal terminals within the MBH, whereas LHRH release, like pituitary LH secretion, is minimally affected by mating in males.

Animals↗