Dopamine Antagonist Domperidone Research Articles

Efficacy of salmon GnRHa, Ovaprim® and hCG for hormonal stimulation of spermiation in the Fowler's toad (Anaxyrus fowleri).

Ex situ amphibian populations can experience reproductive dysfunction due to the absence of environmental cues that trigger reproductive events. Assisted reproductive technologies (ART) for amphibians, specifically exogenous hormone regimens, can circumvent these external signals to induce gametogenesis and gamete release. Currently, the use of the mammalian reproductive hormones gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) are used in a species-specific manner to stimulate amphibian breeding. Hormones or hormone mixtures that are effective in all breeding scenarios would provide the best option for conservation practitioners and some commercial products are already in use for breeding other ectotherms. Ovaprim®, which contains salmon GnRH analogue (sGnRHa) and the dopamine antagonist domperidone (DOM), is effective in fish aquaculture and may be effective for amphibians. To test this hypothesis, we treated Fowler's toads (Anaxyrus fowleri) with either sGnRHa alone, a high or low dose of Ovaprim® or hCG. We then compared spermiation response, sperm quantity and quality parameters, and changes in animal mass over time within each treatment. We found administration of Ovaprim® resulted in more males producing sperm with better motility compared to administration of sGnRHa alone. In addition, the Ovaprim® and sGnRHa treatments resulted in lower response rates, lower sperm motilities, more abnormal sperm, and higher aggregations of sperm compared to the hCG treatment. Furthermore, Ovaprim®-treated males gained significant mass, suggesting an anti-diuretic effect of DOM. Together, these results show that neither Ovaprim® nor sGnRHa, at the concentrations tested, are likely suitable replacements for hCG in ex situ bufonid breeding programmes and that hormone mixtures developed for fish may have limited transferability to new world toad species.

Prolactin and the swine mammary gland

Prolactin is a hormone that is most important for mammary development in swine. It is also essential for both the onset and the maintenance of lactation. In early studies, exogenous recombinant porcine prolactin was used to detect its biological effects on mammary tissue. In these studies, a stimulatory role of prolactin for mammary development of prepubertal gilts was demonstrated. However, when injected throughout lactation, prolactin did not increase sow milk yield likely because mammary receptors were saturated. The secretion of prolactin is largely under negative regulation via dopamine. Inhibition studies using the dopamine agonist bromocriptine showed that prolactin is required in the last third of gestation to sustain mammary development in gilts. When creating a hyperprolactinemic state during that same period, with the dopamine antagonist domperidone, differentiation of mammary epithelial cells was stimulated and milk yield in the subsequent lactation was increased. Domperidone given throughout lactation also led to greater milk yield. A study using domperidone in prepubertal gilts, however, did not reproduce the stimulatory effect of exogenous prolactin on mammary development and demonstrated that timing of the prolactin increase in relation to age of the animals is most important to elicit a response on mammary tissue. Attempts were made to use feed ingredients such as the plant extract from milk thistle, sylimarin, to stimulate prolactin secretion in sows. However, even though prolactin concentrations were increased, this augmentation was not important enough to have an impact on mammary development in late gestation or to increase milk yield. The current knowledge that hyperprolactinemia has beneficial effects for mammary development at various physiological stages and can enhance milk yield in swine leads to new avenues in elaborating strategies that could be used at the farm level to improve sow lactation performance.

Artificial Reproduction and Embryogeny of the Tiger Frog Hoplobatrachus occipitalis (Günther 1858)

The objective of this study was to investigate the embryonic development of the frog Hoplobatrachus occipitalis after their artificial reproduction with the Ovaprim®, a combination of gonadotropin releasing hormone analogue and dopamine antagonist domperidone. Male and female H. occipitalis were collected from the wild and were intramuscularly injected with Ovaprim® at doses of 6 µL/g and 8 µL/g body weight, respectively. The eggs were laid 6 h after hormone injection. The numbers of eggs laid by each female frog were 1726 ± 5.4 (SD) with 94.4% and 88.2% mean fecundity and hatching rate, respectively. The diameter of the eggs at laying was 2.73 ± 0.33 mm while it was 5.04 ± 0.05 mm just before hatching. The stages of embryonic development starting from fertilization to tadpoles’ formation took 27 h to complete at 26.4 ± 0.3 °C. The average height of the tadpoles after hatching was 5.1 mm. Circular tadpole movement in the chorion with an irregular respiratory movement was observed at 21 h after egg-laying. In summary, the study shows that H. occipitalis could reproduce in controlled environment by hormonal induction; the reproductive structures have no significant effect on egg-laying; and the embryonic development time of H. occipitalis differs from that other Anuran species.

Effects of milking frequency and domperidone injections on milk production and prolactin signaling in the mammary gland of dairy cows

Eleven mid-lactation Holstein cows were milked twice daily during the first 2 experimental weeks. During wk 3 to 10, the cows were differentially milked: right quarters were milked thrice daily (3×) and left quarters were milked once daily (1×). During wk 11 to 14, all quarters were milked twice daily. After 4 wk of differential milking, the cows received daily i.m. injections of the dopamine antagonist domperidone (DOMP; 300 mg; n = 6) or of dimethyl sulfoxide as the control (CTL; n = 5) for 8 wk (wk 7-14). During the differential milking period (wk 3-6), milk production was greater for quarters milked 3× than for those milked 1× but did not differ between DOMP and CTL cows. During the differential milking + injection period (wk 7-10), milk production continued to differ according to milking frequency. However, DOMP injection did not have an effect or interact with milking frequency on milk production. During the injection period (wk 11-14), milk production remained greater in the quarters previously milked 3× and milk production increased in DOMP injected cows but not in CTL cows. Injections of DOMP increased prolactin concentration, which was greater in the serum of DOMP cows than in that of CTL cows during the differential milking + injection and the injection periods. The expression of genes that are directly related to milk synthesis (CSN2, LALBA, and ACACA) was greater in the 3× quarters than in the 1× quarters. In addition, DOMP increased CSN2 expression during the injection period. The expression of both isoforms of the PRLR gene was greater in the 3× quarters during the differential milking + injection and the injection periods. At the protein level, injections of DOMP tended to increase the number of long PRLR isoform during the differential milking + injection period. The number of short PRLR isoform was greater in the 1× quarters than in the 3× quarters during the differential milking, the differential milking + injection, and the injection periods. The total amount of STAT3 protein was greater in the 1× quarters during the differential milking and the differential milking + injection periods. The amount of phosphorylated STAT3 protein was greater in the 1× quarters during the differential milking period. The total amount of phosphorylated STAT5 protein was greater in the 3× quarters during the differential milking and the differential milking + injection periods. The results of this experiment support the hypothesis that the responsiveness of the mammary gland to PRL is modulated by milking frequency, although the underlying mechanism remains to be determined.

Domperidone treatment advances onset of puberty in the viviparous mosquitofish Gambusia affinis

BackgroundAlthough dopamine (DA) exerts modulatory effect on reproduction in the majority of fishes, its role is not clearly understood in viviparous species. The aim of this investigation was to determine the influence of DA antagonist domperidone (DOM) on puberty in the viviparous species Gambusia affinis.ResultsTreatment of 1.5 or 4 mg DOM to 25 days post-hatching (DPH) juveniles for a period of 35 days resulted in dense aggregations of gonadotropin-releasing hormone (GnRH)-immunoreactive fibres in the proximal pars distalis (PPD) region of the pituitary gland in contrast to faintly seen fibres in treatment controls. In the ovary, the follicles belonging to stages I–IV did not differ significantly among different experimental groups. However, stage V (vitellogenic) follicles were completely absent in treatment controls in contrast to their presence in 1.5 or 4 mg DOM-treated fish. Besides, the diameter of stage V follicles was significantly higher in 1.5 mg DOM-treated fish compared with 4 mg DOM-treated fish.ConclusionsThe results suggest that DOM treatment triggers the follicular development and promotes the early onset of puberty, possibly by attenuating the dopaminergic inhibition on GnRH fibres, for the first time in a viviparous species.

Evaluation of cGnRH IIa for induction spawning of two ornamental Synodontis species

Efficacy, reliability, and safety are of principal concern for spawning aids used in reproduction protocols for aquaculture species. Ovaprim®, a salmon gonadotropin releasing hormone analog (sGnRH IIIa, D-Arg6-Pro9-Net, 20 μg/mL) and a dopamine antagonist (Domperidone, 10 mg/mL), is currently the preferred choice for induction spawning of ornamental fishes. However, this preparation may be unreliable or completely ineffective in some cases. cGnRH IIa (D-Arg6, Pro9-NHet) has garnered recent interest as an alternative GnRH subtype which offers increased biological activity, reliability, and may ultimately help to increase on farm productivity and expand the diversity of species able to be cultured. The objective of this study was to evaluate the efficacy of cGnRH IIa and Ovaprim® on various quantitative and qualitative measures of spawning performance in Synodontis nigriventris and Synodontis eupterus.Four hormone doses were evaluated (50, 100, 200 μg/kg cGnRH IIa; 10 μg/kg sGnRH IIIa), each of which also contained an equal concentration of a dopamine antagonist (5 mg/kg domperidone). Fish were palpated to check for ovulation at 16, 20, and 24 h post injection. Upon successful ovulation, eggs were manually stripped, weighed, and fertilized. A subsample was photographed under a dissecting microscope for subsequent determination of fertilization success and egg diameter. Hatching success for individual spawns was calculated from subsamples of fertilized eggs stocked into hatching containers.Results indicated similar ovulation success among the four hormone treatments at the 16, 20, and 24 h time periods. Total fecundity, fertilization, embryo diameter, hatching success, larval notochord length, and larval mortality did not vary significantly among treatments. These results suggest that cGnRH IIa exhibits comparable spawning performance to the industry standard Ovaprim®, for induced spawning of S. nigriventris and S. eupterus.

Effect of Dopamine antagonist (Domperidone) treatment on induction of ovulation in anestrous mares

The current study is an endeavor for profound understanding some hormonal and biochemical constituents during induction of ovulation in anestrous mares by using domperidone (Dopamine antagonist). Fifteen anestrous pure Arabian mares divided randomly into 2 groups, group (1) five mares and serve as a control, while Group (2) ten mares treated with 1.1 mg/kg domperidone for 25 days. Ultrasonographic scan was performed twice per week for detection of ovarian activity and follicular growth. Blood samples were collected one month before the treatment for 3 times with 10 days intervals for detection of progesterone, and twice per week after treatment till 10 days after the end of treatment for determination of progesterone, estrogen and prolactin hormones in addition to total protein, total cholesterol and triglycerides, before and after response for treatment. Eight mares (80%) showed ovulation and CL formation from the domperedone treated group while 2 mares (20%) showed no large follicles formation till the end of the trial period. The obtained results showed a significant increase in progesterone, estradiol and prolactin concentration in treated group compared to control one at 3rd and 4th week from treatment, while cholesterol level showed significant increase in treated group compared to control at 3rd week of treatment. And non significance change was recorded in protein and triglycerides levels. We can conclude that using Dopamine antagonist (Domperidone) is effective alternative for induction of ovulation in anestrous Arabian mares under Egyptian circumstances.

New insights into the importance of prolactin in dairy ruminants

In most mammals, prolactin (PRL) is essential for maintaining lactation, and the suppression of PRL inhibits lactation. However, the involvement of PRL in the control of ruminant lactation is less clear, because inconsistent effects on milk yield have been observed with the short-term suppression of PRL by bromocriptine. Therefore, several experiments have been conducted to assess the galactopoietic role of PRL. In an initial experiment, cows in early lactation received daily injections of the dopamine agonist quinagolide for 9wk. Quinagolide reduced milking-induced PRL release and caused a faster decline in milk production. Quinagolide also reduced mammary epithelial cell activity, survival, and proliferation. In goats, cabergoline, another dopamine agonist, caused a 28% decrease in milk yield the day after injection. In another experiment, cows were injected for 5d with quinagolide, with quinagolide plus bovine PRL injected at milking time, or with vehicles only. Again, quinagolide reduced milk, protein, and lactose yields. Although PRL injections were not sufficient to restore milk yield, they tended to increase milk protein and lactose yields and increased the viability of mammary epithelial cells purified from milk. Recently, our team stimulated PRL secretion with daily injections of the dopamine antagonist domperidone for 5wk. Milk production increased gradually and was greater in domperidone-treated cows during the last 4wk of the treatment period. In most experiments where PRL secretion was manipulated, feed intake paralleled the changes of PRL concentration, supporting the idea that PRL increases feed intake to provide the nutrients necessary to support lactation in dairy ruminants. In late-lactation cows, quinagolide and cabergoline decreased milk production within the first day of treatment and induced more rapid changes in several markers of mammary gland involution after drying-off. In addition, quinagolide improved the resistance to intramammary infection, suggesting that PRL inhibition could be an alternative strategy for facilitating drying-off. Prolactin appears to directly affect mammary gland functions, but mammary gland responsiveness to PRL appears to be modulated by local and systemic factors. Therefore, the modulation of the number and isoforms of the PRL receptors as well as the expression of intracellular modulators of cell signaling in the mammary gland require further investigation. In conclusion, these data, combined with those from other studies, provide a good body of evidence that PRL is galactopoietic in dairy ruminants.

The dopamine antagonist domperidone increases prolactin concentration and enhances milk production in dairy cows

In previous studies, our team showed that the inhibition of prolactin (PRL) secretion by the dopamine agonist quinagolide reduces milk production in dairy cows. The objective of this study was to determine the effects of administration of a dopamine antagonist on basal and milking-induced PRL concentrations in blood and on milk production during positive energy balance and feed restriction in dairy cows. Eighteen mid-lactation Holstein cows received daily s.c. injections of either domperidone (300mg, DOMP, n=9) or the vehicle, canola oil (CTL, n=9), for 5wk. During wk 5, all cows were fed at 65% of their dry matter intake in the previous week. Blood and milk samples were collected before (for blood) and during (for milk) the a.m. milking thrice weekly from d −9 to 41 (8d after the last injection). In addition, blood samples were collected during the a.m. milking on d −1 (before the first injection), and on d 1, 28, and 34. Basal PRL concentration was similar in both groups before the start of the treatments. Domperidone injections caused a gradual increase in basal PRL concentration. Feed restriction reduced basal PRL concentration in both the CTL and DOMP cows, but PRL concentration remained higher in the DOMP cows. Prolactin concentration remained elevated in the DOMP cows 7d after the last injection. The milk concentration of PRL increased during the DOMP treatment, but the increase was smaller than that observed in serum. In the CTL cows, the milking-induced PRL release above the premilking concentration was similar on d −1, 1, and 28 but was reduced during feed restriction. In the DOMP cows, the milking-induced PRL release was similar on d −1 and 1 but was reduced on d 28 and 34. Milk production was similar for both groups before the treatments started but was greater in the DOMP cows during the treatment period, at 2.9±0.6 and 2.4±0.6kg/d greater during wk 3 and 4 of treatment, respectively. Milk production declined in both groups during feed restriction but remained higher in the DOMP cows. Milk production became similar again for both groups after the last injection. In addition, dry matter intake was increased by DOMP. These results support the hypothesis that PRL is galactopoietic in dairy cattle.

Recent advances in the use of an estradiol-dopamine antagonist protocol to induce ovulation in seasonally anovulatory mares

The January 1 birthday imposed by major breed registries is in conflict with the natural breeding season of the mare. Without intervention, breeders are denied the documented advantages in price and performance of foals born earlier in the year [1]. Dopamine antagonists have been used to induce early ovulation in anovulatory mares [2,3,4,5]. Kelley and associates [6] were the first to report the enhancement of prolactin secretion and superior advancement of first ovulation by pretreatment with estradiol benzoate prior to the administration of dopamine antagonist. The protocol described by Kelley et al. (6) was streamlined by Thompson et al. [7], who found that a single injection of estradiol cypionate (ECP) gave consistent prolactin and luteinizing hormone responses equivalent to those observed by Kelley et al. [6]. Subsequently, it was shown that a single injection of ECP followed by a single injection of the dopamine antagonist domperidone advanced first ovulation in anovulatorymares inwinter [8], although with a lower success rate than the earlier, more complicated protocols. The experiments described herein were conducted to assess potential improvements in the ECP-dopamine antagonist protocol for inducing ovulation in seasonally anovulatory mares.

Late gestational hyperprolactinemia accelerates mammary epithelial cell differentiation that leads to increased milk yield1

The growth rate of piglets is limited by sow milk yield, which reflects the extent of epithelial growth and differentiation in the mammary glands (MG) during pregnancy. Prolactin (PRL) promotes both the growth and differentiation of the mammary epithelium, where the lactational success of pigs is absolutely dependent on PRL exposure during late gestation. We hypothesized that inducing hyperprolactinemia in primiparous gilts during late gestation by administering the dopamine antagonist domperidone (DOM) would increase MG epithelial cell proliferation and differentiation, subsequent milk yield, and piglet growth. A total of 19 Yorkshire-Hampshire gilts were assigned to receive either no treatment (CON, n = 9) or DOM (n = 10) twice daily from gestation d 90 to 110. Serial blood sampling during the treatment period and subsequent lactation confirmed that plasma PRL concentrations were increased in DOM gilts on gestation d 91 and 96 (P < 0.001). Piglets reared by DOM-treated gilts gained 21% more BW during lactation than controls (P = 0.03) because of increased milk production by these same gilts on d 14 (24%, P = 0.02) and 21 (32%, P < 0.001) of lactation. Milk composition did not differ between the 2 groups on d 1 or 20 of lactation. Alveolar volume within the MG of DOM-treated gilts was increased during the treatment period (P < 0.001), whereas epithelial proliferation was unaffected by treatment. Exposure to DOM during late gestation augmented the postpartum increase in mRNA expression within the MG for β-casein (P < 0.03), acetyl CoA carboxylase-α (P < 0.01), lipoprotein lipase (P < 0.06), α-lactalbumin (P < 0.08), and glucose transporter 1 (P < 0.06). These findings demonstrate that late gestational hyperprolactinemia enhances lactogenesis within the porcine MG and increases milk production in the subsequent lactation.

Enhancing Ovulation of Malaysian Mahseer (Tor tambroides) in Captivity by Removal of Dopaminergic Inhibition

Natural spawning ground of most Malaysian streams are undergoing extreme changes as a result of human activities, pollution and climate change (extreme temperature fluctuation) which lead to dramatic decrease in mahseer (Tor tambroides, Cyprinidae) populations. An experiment was conducted to evaluate the effectiveness of salmon gonadotropin releasing hormone analogue (sGnRHa) alone or in combination with dopamine antagonist domperidone (DOM) on breeding performances of female breeders. Sixty females T. tambroides ranging in weight 2.01 to 3.96 kg while thirty males with average weight 1.38 to 1.72 kg were used in this study. The females were given pretreatment with Ovaplant (23.4-44.9 μg kg-1) for 6 weeks prior to induction. Females were tested with various treatments such as Ovatide, sGnRHa, sGnRHa+DOM and DOM. SGnRH analogue alone does not contain dopamine antagonist to block dopaminergic inhibition action. Females were given single intramuscular injection of Ovatide (0.5 mL kg-1 BW), sGnRHa (10 μg kg-1 BW), sGnRHa+DOM (10 μg kg-1 BW+5 mg kg-1 BW) or DOM (5 mg kg-1 BW). The control group was administered with 0.9% NaCl. The fish did not spawn spontaneously but through hand stripping to release eggs. Results showed that Ovatide significantly produced highest ovulation rate, total stripped eggs and stripped fecundity. Interestingly, we observed that broodstock groups injected with sGnRHa+DOM produced highest fertilization, hatching and survival rates compared to other treatments. Good egg and larval quality were recorded in the group treated with sGnRHa+DOM. No females ovulated in the group receiving DOM alone and saline solution. The combination treatment was found to be more potent in inducing ovulation as compared to sGnRHa alone or DOM alone. Our results suggest that dopaminergic inhibition is a major barrier in inducing spontaneous spawning in captive mahseer and we successful produced progeny generation of T. tambroides larvae.

Induced Volitional Spawning and Larval Rearing of Pinfish

AbstractAquaculture of marine baitfish is still in its infancy. Induced spawning of marine baitfish species has the potential to supplement this seasonal capture fishery and offer a consistent supply to anglers. The pinfish Lagodon rhomboides has been identified as a species with potential for commercial production, yet few studies have focused on the induced spawning and larval rearing of this baitfish. The purpose of this study was to evaluate the efficacy of using Ovaprim, composed of a salmon gonadotropin‐releasing hormone analog (sGnRHa) and a dopamine antagonist (domperidone), to induce volitional spawning in pinfish. Additionally, a preliminary larval feeding regime was investigated, and growth and development of pinfish larvae were documented. A single dose of 0.50 mL of Ovaprim per kilogram of fish (sGnRHa: 20 μg/mL; domperidone: 10 mg/mL) was sufficient to induce volitional spawning 36–48 h after intraperitoneal injection of female pinfish. Observed fecundity was 2,565 eggs/female (13.1 eggs/g), and larval survival ranged from 10% to 117% through 33 d posthatch (DPH). Larvae were observed to have completed swim bladder inflation by 19 DPH, with 100% percent of larvae exhibiting notochord flexion by the same date. This represents the first published study in which protracted larval rearing was successfully achieved after induced volitional spawning of pinfish.

Effects of GnRHa (D-Ala 6, Pro 9-NEt) combined with domperidone on ovulation induction in wild loach Misgurnusanguillicaudatus

The effects of a single intramuscular injection of gonadotropin releasing hormone analogue (GnRHa) alone or in combination with the dopamine antagonist domperidone (DOM) on ovulation induction of loach Misgurnus anguillicaudatus broodstocks collected from the wild were tested under routine hatchery conditions. The ovulation ratio, latency period, ovulation index, fertilization success and hatching rate were evaluated. The following hormone treatments were tested: 2 mg kg − 1 BW of CPE as a positive control (PC), GnRHa alone at doses of 10 µg (G10), 20 µg (G20), 40 µg (G40) and 60 µg (G60) kg − 1 BW and combinations of GnRHa and DOM at doses of 5 µg + 2.5 mg (GD5), 10 µg + 5 mg (GD10), 20 µg + 10 mg (GD20) and 40 µg + 20 mg (GD40) kg − 1 , respectively. Physiological saline injected fish were used as a negative control (NC). The results showed that the combination of 20 µg + 10 mg (GD20) and 40 µg + 20 mg (GD40) kg − 1 of GnRHa and DOM, respectively, injection led to higher ovulation ratio and shorter latency periods in comparison with the control and the other hormone treatments ( P < 0.05), and there was no significant difference between the two ovulating groups with respect to ovulation ratio and latency period ( P > 0.05). There was a significant difference between the GnRHa alone groups and the GnRHa + DOM combined groups on the ovulation index (the former < the latter, P < 0.05), while no significant differences in the fertilization success and hatching rate were found in any of the hormone treatments ( P > 0.05). Only 20% of the fish ovulated in group G10 and G20, and no fish ovulated in group NC, suggesting a dopaminergic inhibitory action on gonadotropin (GtH) secretion in this fish at the preovulatory stage. Therefore, it can be concluded that like many other cyprinids, dopamine inhibitory action was operating in loach and it was necessary to combine GnRHa with a dopamine antagonist for ovulation induction. As a result, ovulation can be induced successfully in loach broodstocks with 20 µg kg − 1 GnRHa + 10 mg kg − 1 DOM treatment in a single injection without any negative effect on egg quality. Application of this combination could be beneficial for hatchery and broodstock management in loach culture.

In vitro Macrophage Activity: Biphasic Effect of Prolactin and Indirect Evidence of Dopaminergic Modulation

Objective: Prolactin (PRL), a peptide hormone produced by the pituitary gland, is involved in the interaction between the neuroendocrine and immune system. Since dopamine receptor antagonists increase serum levels of PRL, both PRL and dopamine receptors might be involved in the modulation of macrophage activity, providing means of communication between the nervous and immune systems. This study evaluated the effects of PRL and the dopamine antagonist domperidone (DOMP) on macrophage activity of female rats. Methods: Oxidative burst and phagocytosis of peritoneal macrophages were evaluated by flow cytometry. Samples of peritoneal liquid from female rats were first incubated with PRL (10 and 100 nM) for different periods. The same procedure was repeated to evaluate the effects of DOMP (10 and 100 nM). Results: In vitro incubation of macrophages with 10 nM DOMP decreased oxidative burst, after 30 min, whereas the PMA-induced burst was decreased by DOMP 10 nM after 2 and 4 h. Treatment with PRL (10 and 100 nM) for 30 min decreased oxidative burst and rate of phagocytosis (10 nM). After 2 h of incubation, 10 nM PRL decreased oxidative burst and phagocytosis intensity, but increased the rate of phagocytosis. On the other hand, after 4 h, PRL 10 and 100 nM increased oxidative burst and the rate of phagocytosis, but decreased intensity of phagocytosis. Conclusions: These observations suggest that macrophage functions are regulated by an endogenous dopaminergic tone. Our data also suggest that both PRL and dopamine exert their action by acting directly on the peritoneal macrophage.

Induced spawning of kutum, Rutilus frisii kutum (Kamenskii, 1901) using (D-Ala 6, Pro 9-NEt) GnRHa combined with domperidone

Kutum, Rutilus frisii kutum (Kamenskii, 1901), Cyprinidae is an endemic fish of the Caspian Sea. The Iranian Fisheries Organization (Shilat) produces up to 200 million fry (1–2 g b.w.) to restock the Caspian Sea population annually. These fish are produced by artificial breeding using carp pituitary extract (CPE). The objective of this study was to assay the effectiveness of a gonadotropin releasing hormone analogue (D-Ala 6, Pro 9-NEt GnRH) alone or in combination with the dopamine antagonist domperidone (DOM) on spawning success, latency period, ovulation index (OI), weight of stripped egg mass/weight of stripped egg mass + remnant ovaries, and fertilization success in kutum. Ninety fish were divided into nine groups and injected intraperitoneally as follows: 2 mg kg − 1 b.w. of CPE as positive control, 20 μg GnRHa kg − 1 b.w. in single injection, 5 μg + 2.5 mg, 10 μg + 5 mg and 20 μg + 10 mg kg − 1 b.w. of GnRHa + DOM in single or double injection (10–90%) 24 h apart. Propylene glycol injected fish were used as negative controls. The results showed that the highest doses of GnRHa and DOM in single injection lead to higher spawning success and latency periods in comparison with positive control ( P < 0.05), while no significant differences in the OI and fertilization success were found ( P > 0.05). Only 2/10 fish were ovulated in the group which received GnRHa 20 μg kg − 1 b.w. alone suggesting dopaminergic tone on gonadotropin (GtH) secretion in this fish at the preovulation stage. Therefore, it can be concluded that like many other cyprinids, dopamine inhibitory tone is active in kutum and it is necessary to combine GnRHa with a dopamine antagonist for spawning induction.

Secretoneurin stimulates goldfish pituitary luteinizing hormone production

Secretoneurin (SN), a 33-34 amino acid neuropeptide is derived from endoproteolysis of secretogranin II (SgII), a member protein of the chromogranin family. SN is widely distributed in various tissues of vertebrates especially in pituitary and hypothalamus, and is a potential new hormone. In vivo, i.p. injection of SN increased luteinizing hormone (LH) release in goldfish pretreated with the dopamine antagonist domperidone. In 6-h static incubation of goldfish pituitary fragments, 10 and 100 nM but not 1 nM concentrations of goldfish SN had a direct stimulatory effect to increase LH release by 2.3- and 1.5-fold (p<0.05), respectively. In addition, 500 nM SN induced a 2.6-fold increase in LHbeta subunit messenger RNA (mRNA) levels in pituitary fragments, regardless of whether LHbeta mRNA levels were expressed relative to 18S ribosomal RNA or beta-actin mRNA. We suggest that the stimulatory actions of SN on LH release may be a part of a paracrine or autocrine feedback loop in the pituitary.

The effect of intracerebroventricular dopamine administration on the respiratory response to hypoxia.

Acute hypoxia produces an increase in ventilation. When the hypoxia is sustained, the initial increase in ventilation is followed a decrease in ventilation. The precise mechanism of this decline in ventilation during sustained hypoxia is unknown. Recent studies hypothesized that the accumulation of dopamine in the central nervous system might have a major role in production of hypoxic respiratory depression. The purpose of this study was to examine whether dopamine has an effect on occurance of central ventilatory depression which is seen in acute hypoxia in peripheral chemoreceptors denervated animals. The experiment were conducted in rabbits anesthetized with Na-pentobarbital (25 mg x kg(-1) i.v.). For intracerebroventricular (i.c.v.) injections of dopamine (1 microg) in each animal, canula was placed in left lateral cerebral ventricle by stereotaxic method. Respiratory frequency (f x min(-1)), tidal volume (V(T)) ventilation minute volume (V(E)) and systemic arterial blood pressure (BP) were recorded during air and 3 minutes hypoxic gas mixture (8%O2-92%N2) breathing. I.c.v. administration of dopamine during normoxia decreased V(T), f, V(E) and BP, significantly. When rabbits were injected with an i.c.v. dopamine on hypoxic gas mixture breathing in control animals, there was depression of hypoxic ventilatory responses. After i.c.v. administration of dopamine antagonists haloperidol (0.1 mg) and domperidone (0.07 mg) in chemodenervated rabbits, the significant increases in V(T), V(E) and BP were observed. On the breathing of hypoxic gas mixture of chemodenervated and i.c.v. dopamine antagonists administrated rabbits, hypoxic depression was completely abolished. These results of this study show that accumulation of dopamine in the brain seems to reduce the response of the central control mechanisms to chemoreceptor impulses during normoxia and hypoxia. In conclusion present study suggests important role played by central dopaminergic pathways in the occurence of acute hypoxic ventilatory depression.

Modulation of pituitary dopamine D1 or D2 receptors and secretion of follicle stimulating hormone and luteinizing hormone during the annual reproductive cycle of female rainbow trout.

The two gonadotrophins follicle stimulating hormone (FSH) and luteinizing hormone (LH) have distinct temporal expression and release profiles in fish, but little is known regarding their neuroendocrine control, especially for FSH. The present experiments were performed on previtellogenic, mature and preovulatory female trout. The catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine, increased plasma LH and FSH concentrations of mature fish. The dopamine agonist apomorphine decreased and the dopamine antagonist domperidone increased plasma LH concentration of preovulatory fish and delayed ovulation, but did not modify plasma FSH concentration. The dopamine D2 agonist bromocryptine inhibited LH release in cultured gonadotrophs from mature and preovulatory fish, but not from previtellogenic fish. Bromocryptine also significantly inhibited basal and salmon gonadotrophin releasing-hormone (sGnRH)-induced FSH release from cultured gonadotrophs of mature fish, but not of preovulatory fish, and increased FSH release from gonadotrophs of previtellogenic fish. The dopamine D1 agonist SKF 38393 had no observed effect on the release of FSH and LH, at any reproductive stage studied. The D1 agonist SKF 38393, the D2 agonist bromocriptine and sGnRH had no observed effects on cell contents of FSH and LH. Taken together, these data suggest that, at the level of the pituitary, dopamine inhibits LH release as vitellogenesis proceeds, via activation of dopamine D2 receptors. We demonstrate for the first time in fish a control of FSH release (a dopamine control), especially in mature fish which have low circulating concentrations of FSH.

Transdermal administration of piribedil reverses MPTP-induced motor deficits in the common marmoset.

The ability of transdermal administration of the dopamine D2/D3 agonist piribedil (1-[3,4-methylenedioxybenzyl)]-4-[(2-pyrimidinyl)]piperazine) to reverse hypokinesia and other motor deficits observed in MPTP-treated common marmosets was investigated. Piribedil (2.5-10.0 mg/animal), applied directly to the skin of the abdomen as a paste, produced a long-lasting and concentration-dependent reversal of motor deficits. The antiparkinsonian actions of piribedil occurred within 10 minutes of drug administration and lasted as long as 10 hours. Transdermally applied piribedil produced a pattern of locomotor activity characteristic of normal motor behavior in this species. Symptoms of nausea (marked excessive salivation, retching, and/or vomiting) were not observed after transdermal application of piribedil. Additionally, pretreatment with the peripheral dopamine antagonist domperidone enhanced the antiparkinsonian effects of piribedil. Application to the skin of monolayer or bilayer patches impregnated with piribedil also produced a marked increase in locomotor activity and reversal of motor deficits. After application of various patch fractions (whole, one-half, or one-fourth), the increase in locomotor activity and reversal of disability correlated well with the surface area of skin covered. Measurement of serum levels of piribedil after single application of bilayer patches showed a positive relationship between drug levels and antiparkinsonian activity. Repeated daily application of piribedil bilayer patches for 5 days to MPTP-treated common marmosets primed to show dyskinesia by previous exposure to L-Dopa produced antiparkinsonian activity accompanied by dyskinetic movements. Transdermal administration of dopamine agonists such as piribedil may provide a useful means of producing a long-lasting reversal of motor deficits in Parkinson's disease while avoiding acute adverse effects such as nausea.