Effects of Infertility by Cabergoline on Serum Sex Hormones and the Inter- and Intra-Sexual Social Behaviors of Female Rattus losea

Jiao Qin, Qian-Qian Su and Quan-Sheng Liu*

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, 105 Xin’gang Xilu, Haizhou, Guangzhou 510260, China

ABSTRACT

Lesser rice-field rat is one of major pests in eastern and southern Asia, causing considerable losses in rice, vegetables, and other crops. The more serious situation was that R. losea has developed high resistance to anticoagulants with repeated and long-term application of anticoagulant rodenticides in southern China. Fertility control is considered as an alternative strategy for management of this pest. Cabergoline can inhibit prolactin (PRL) secretion and was applied in fertility control for animal, however, the physiological and behavioral mechanisms of cabergoline as a sterilant in practice remain little known. This study determined the effects of different doses of cabergoline on the inter- and intra-sexual social behavior and reproduction physiology in adult female lesser rice-field rats, Rattus losea. Results showed that the ovary weight of female rats treated with cabergoline significantly increased at day 24, but there were no notable changes in the uteri regardless dosage and time. PRL in female rats treated by 50 µg/kg cabergoline significantly was decreased by 56% at day 7 compared with the control. However, estradiol (E2) in rats treated with 50 µg/kg cabergoline was higher than that in control group at day 24, and progesterone (P) secretion was not remarkably influenced by cabergoline. Moreover, the duration of investigation toward normal females in the 50 µg/kg groups at day 3 exceeded that of pre-treatment. The females treated by 100µg/kg cabergoline increased the frequency of investigation towards normal females and self-grooming and resting than pre-treatment. The duration of female investigation and defense towards normal males was lower in the 50-µg/kg groups at day 7 than the untreated group. Collectively, these data indicated that cabergoline might increase the amiable and sexual motivation behaviors of female R. losea, which implied that female rats sterilized by cabergoline still might keep the capacity of competitive reproductive interference.

Article Information

Received 10 January 2019

Revised 01 March 2019

Accepted 30 April 2019

Available online 26 March 2020

Authors’ Contribution

LQS designed the research. QJ, SQQ and LQS performed the experiment. QJ and LQS analyzed data and wrote the paper.

Key words

Cabergoline, Fertility control, Prolactin, Sterilant, Rattus losea.

DOI: https://dx.doi.org/10.17582/journal.pjz/20190110070138

* Corresponding author: [email protected]

0030-9923/2020/0004-1309 $ 9.00/0

Copyright 2020 Zoological Society of Pakistan

INTRODUCTION

Rodents remain among the world’s most important pests (Munawar et al., 2018; Buckle and Smith, 2015; Prakash, 1988; Singleton et al., 1999), and are reservoirs for devastating human diseases (Brown et al., 2017). The lesser rice-field rat (Rattus losea) is such one of main nuisances, which causes considerable agricultural damage in eastern and southern Asia, mainly in southern China, Laos, Thailand, and Vietnam, and is an important reservoir of numerous pathogens, such as plague (Liu et al., 2010; Yang et al., 2006; Zhang and Wang, 1998). So far, R. losea still continues to bring about substantial losses to food crops such as rice, despite advances in methods of control and management techniques. In more serious cases, R. losea has developed high resistance to anticoagulants with repeated and long-term application of anticoagulant rodenticides in south China (Wang et al., 2008). Thus, effective, safe, and sustainable pest control drug and methods that can control the growth of anticoagulant-resistant rodent populations should be developed.

The success of the pest rodent species can be attributed to their short lifespan, high rates of fecundity (high litter sizes, short gestation period and short duration to sexual maturity), potential to disperse long distances, complex social hierarchy, flexible social systems and their physiology and body structure which allow them to live in a wide range of environments (Buckle and Smith, 2015; Prakash, 1988). Traditional culling by baiting aims to increase the mortality rate of animal population and consequently decrease population numbers; however, it usually results in rapid population recovery as a result of the ‘population bound effect’ (Ericson, 1970), environmental contamination, and risks to non-target species (Zhang, 2000). As second-generation pest management strategy (Krebs, 2014), fertility control aims at reducing birth rates of animal populations and overcoming the problems associated with traditional culling. Moreover, better control effect could be achieved by contraception than by simple culling when the ‘competitive reproductive interference’ is taken into account, since sterile individuals continue to draw on vital resources and could participate in mating competition (Caughley et al., 1992; Chen et al., 2017; Li et al., 2019; Liu et al., 2012; Liu et al., 2013; Qin et al., 2017; Shi et al., 2002; Wang et al., 2011; Zhang, 2000). In the light of complex social hierarchy and mating system of rodents, the behavioral mechanisms underlying competitive reproductive interference are very sophisticated and multifarious. However, whether the ability to attract heterosexual individuals of sterilized female or male is impaired or maintained remain little unknown. The extant knowledge gap in behavioral mechanisms currently limits our capacity to assess objectively and comprehensively the potential of sterilants, though the mechanism is critical for the effects of fertility control.

Cabergoline a dopamine agonist, can effectively suppress prolactin (PRL) secretion (Post et al., 1988). Cabergoline has also been introduced to interfere with early gestational processes that require PRL in dogs (Jöchle et al., 1989; Post et al., 1988), cats (Jöchle et al., 1989), rats (Ferraro et al., 1995), foxes (Marks et al., 2001), mouse (Su et al., 2013, 2014), and other wild animals (Hearn et al., 1998; Qin et al., 2015a,b, 2017), and prevent females from lactating for a long period (Amenomori et al., 1970; Bachelot and Binart, 2007; Ben-Jonathan et al., 2008; Freeman et al., 2000; Marks et al., 2001; Mednick et al., 1980). As a potential sterilant for pest rodents, cabergoline possesses certain advantages, including action in both sexes, low dosages, and long-lasting effect (Ferraro et al., 1995; Qin et al., 2015a,b, 2017; Su et al., 2013, 2014). Nevertheless, the effects of cabergoline on social behaviors of animals and possibly on endocrine mechanism remain elusive.

In male R. losea, cabergoline reduces their serum luteinizing hormone, the sperm quality, and enzyme activity in testis (Qin et al., 2015a,b), and decline times of aggression and investigation to normal male, but does not change times of investigation to normal female (Qin et al., 2017). This implied that male R. losea sterilized with cabergoline still hold some opportunity to interfere reproduction of normal rats, since the mating system of R. losea isn’t monogamy (Chen et al., 2011). However, the effects of cabergoline on the physiology and behaviors in female R. losea remain unknown. To study the effect of cabergoline on physiology, we determined the variations of serum PRL, estradiol (E2) and progesterone (P) levels in nonbreeding female R. losea under different doses and times. According to the mechanism of cabergoline action, we predicted that serum PRL would decrease and E2 secretion would increase to consequently reduce the number of dopamine receptors in treated females (Leong et al., 1983). To analyze the effects of cabergoline on the social behaviours of females, we assigned dyadic encounters between treated female with normal male or female. PRL performs a significantly function in regulating the maternal behaviors of females (Freeman et al., 2000). Previous studies clearly indicated that cabergoline suppresses PRL secretion. Thus, we infer that female R. losea would decrease amiable and sexual motivations behaviors.

 

MATERIALS AND METHODS

Animals and materials

Lesser rice-field rats (Rattus losea) used in all trials were trapped on a farmland in Zengcheng, Guangdong (23°18’N, 113°38’E) and then transported to Guangdong Institute of Applied Biological Resources. They were fed the rat pellets (Guangdong Medical Laboratory Animal Center, Guangzhou, China) and water ad libitum. Rats were housed individually in plastic cages (30 cm × 20 cm × 16 cm) and maintained in a cycle of 12 L:12 D (lights on from 08:00 to 20:00) at 24 ± 1 ℃ for 8 weeks prior to the behavior tests. All animal maintenance, trial protocols and sample collection protocols complied with the Institutional Animal Care and Use Committee of Guangdong Institute of Applied Biological Resources, Guangdong Academy of Sciences. Cabergoline (Tocris Bioscience, UK) was dissolved in sunflower oil at a dose of 50 and 100 μg/kg (body weight).

Forty adult females were divided randomly into five groups. There were no significant differences in body weight in five groups (F4,35 = 0.464, P = 0.761, mean body weight ± SE = 97.68 ± 2.76 g). Body weight had positive correlation with age of R. losea, by which female weight in 60-120 g was defined adult (Guo et al., 2014). The control group (C) and four other treatment groups: C, 1.0 ml of oil for 3 consecutive days and tissue collection 24 days later; two groups treated by 50 μg/kg for 3 consecutive days and killed for tissue collection 7 and 24 days later; other two groups treated by 100 μg/kg for 3 consecutive days and killed for tissue collection 7 and 24 days later; which doses and time course were designed according some studies (Negishi and Koide, 1997; Marks et al., 2001; Su et al., 2013, 2014; Qin et al., 2015a,b, 2017). After treatment, each group rats were fed normally. The female rats were weighed (±0.1 g) at 5 d intervals.

Dyadic encounters

The dyadic encounter occurred in a glass box (length × width × height = 80 cm × 40 cm × 80 cm). The box was surrounded by an opaque piece of chipboard to block the interference of each animal. The arena was partitioned into 2 equal compartments (40 cm × 40 cm × 80 cm) by removable cardboard (40 cm × 80 cm), and a rat from each pair was placed in one half of the arena. After a 5 min acclimatization period, the cardboard was removed, and the rats were allowed to interact for 30 min. Behaviors were recorded by digital video recorder. The arena was cleaned with water and 75% ethanol between trials (Liu et al., 2013).

Prior to cabergoline treatment, one female from the pre-treatment groups was assigned to dyadic encounters with one subject from the control group (C-female) on different days. Behaviors were observed for 30 min and videotaped. Forty adult males were assigned to a mating partner (mean body weight ± SE = 107.80±4.34 g, F4,35 = 0.217, P = 0.927, male weight in 60-150 g was defined adult (Guo et al., 2014). To 3 days after the encounter with a C-male, each rat encountered one normal male for 30 min. Females with similar body weights (within 10% difference) were paired up in two combinations in dyadic interactions. Females were treated with cabergoline for 3 days; one individual from post-treatment encountered the same individual from the C-female group on day 4 (1 day after the end of 3-day treatment) and day 21 (18 days after the end of 3-day treatment). Each group experiment was conducted at 3 d intervals.

The behavioral interactions were defined as follows: investigation, aggression, defense, amiable behavior, and self-oriented behavior (Cassaing and Isaac, 2007; Liu et al., 2013). The time and frequency of the above behaviors were recorded.

Hormones and reproductive organs

Female rats were sacrificed by decapitation between 09:00 and 11:00 h on 7 or 24 d after cabergoline treatment. Blood was collected and serum was separated from each blood sample by centrifugation at 4000g for 15min at 4℃, and stored at -80℃ until hormone analysis. E2, P and PRL were quantified by radioimmunoassay using 125I RIA kits (Beijing North Institute of Biological Technology, China). The inter- and intra-assay variations were less than 10% and 15%, respectively. The RIA kits were validated and used for a few wild rodent species following the standard kit instructions (Wang et al., 2006, 2011; Lv and Shi, 2011). Ovaries and uterus were dissected and weighed (±1 mg).

Statistical analysis

The two-way ANOVA was using to examine the effects of dosage and treatment time of cabergoline on serum hormone concentrations, body mass and organ weight. We performed least significant difference (LSD) test to compare the changes among the different groups, particularly between the females in the control group and the treatment group. Behavioral data were statistically analyzed by performing Mann-Whitney U test or Wilcoxon signed-rank test to examine the differences between groups. P < 0.05 was considered significant. The data were presented as means ± SE. Results were analyzed using SPSS 13.0 for Windows.

 

RESULTS

Sex hormones

There were no significant effects of drug dosage (F2,34 = 1.641, P = 0.209) and time course (F2,34 = 2.571, P = 0.091) on the E2 content. However, the E2 concentrations in female lesser rice-field rats treated with 50 µg/kg cabergoline increased by more than three times at day 24 compared with those in the control group (P =0.020, Fig. 1a). Drug dosage and time course did not affect P level (D: F2,32 = 1.041, P = 0.365; T: F2,32 = 1.183, P = 0.319), and there were no differences between all groups (Fig. 1b). Time course (F2,31 = 3.641, P = 0.038), not cabergoline dosage (F2,31 = 1.961, P = 0.158), significantly affected PRL concentration. At 50 µg/kg cabergoline, PRL concentrations decreased significantly by 56% at 7 d compared with those in the control group (P = 0.037) and recovered at day 24 (P = 0.037, Fig. 1c).

Body weight and reproductive organs

The results showed that 50 or 100 µg/kg cabergoline did not change the body weight of females during the entire experiment (P > 0.05). The drug dosage and time course did not affect the wet weight of the ovary (D: F2,35 = 3.262, P = 0.050; T: F2,35 = 1.424, P = 0.254) and uterus (D: F2,35 = 2.017, P = 0.148; T: F2,35 = 0.697, P = 0.505). The ovary of the female rats treated with 50 µg/kg cabergoline at 24 d increased in comparison with those of the control females (P = 0.017 and exceeded those of the rats treated with 100 µg/kg cabergoline at 24 d (P = 0.036, Fig. 2a).

Behavioral interactions in varied groups

Cabergoline also affected the social behaviors of female R. losea. The duration of individual investigation toward normal females was more than two times longer in the 50 µg/kg group compared with that in pretreated group at day 4 after treatment (Z = −2.380, P = 0.017, Table I), whereas the duration of self-grooming and resting simultaneously decreased by 14.5% (Z = −2.240, P = 0.025, Table I). The frequency of self-grooming and resting (Z = −2.173, P = 0.030; Z = −2.028, P = 0.043, Table I) and investigation (Z = −2.313, P = 0.021; Z = −1.973, P = 0.049, Table I) toward normal females increased significantly in the 50 and 100 µg/kg groups compared with the pretreated groups at day 4 after treatment.

The dyadic encounter with normal males, the duration of individual female investigation (Z = −2.313, P = 0.021) and defense were evidently lower in the 50 µg/kg group at day 7 compared with pretreated groups (Z = −2.366, P = 0.018, Table II), whereas the duration of self-grooming and resting decreased by 12.19% (Z = −2.521, P = 0.012, Table II). The frequency of investigative behaviors toward males decreased in females treated with 50 and 100 µg/kg cabergoline at day 7 (Z = −2.524, P = 0.012; Z = −2.383,

 

Table I. Comparison of females’ investigation, aggression, defense and self-grooming and resting times (T, sec) and frequency (F) in 30 min encounters with control females between the control and the treated females.

Dose (µg/kg)	Treated female toward control		Investigation	Aggression	Defense	Self-grooming and resting
50	Pre-treat	T	165.1 ± 37.7B	9.0 ± 9.0	15.0 ± 15.0	1610.9 ± 45.4A
		F	9.8± 1.5b	0.4 ± 0.4	0.5 ± 0.5	10.8 ± 1.5b
	Post-treat day 4	T	366.9 ± 59.6A	0.0 ± 0.0	28.9 ± 19.5	1376.6 ± 87.1B
		F	22.5 ± 3.1a	0.0 ± 0.0	0.3± 0.2	23.5 ± 3.4a
	Post-treat day 21	T	181.0 ± 42.6B	0.0 ± 0.0	0.0 ± 0.0	1610.4 ± 47.3A
		F	11.4 ± 1.4b	0.0 ±	0.0 ± 0.0	11.9 ± 1.5b
100	Pre-treat	T	168.8 ± 42.7	15.0 ± 15.0	9.0 ± 9.0	1607.3 ± 48.2
		F	9.0 ± 2.4b	0.5 ± 0.5	0.4 ± 0.4	9.8 ± 2.3b
	Post-treat day 4	T	214.8 ± 30.6	0.0 ± 0.0	32.5 ± 32.5	1552.8 ± 19.2
		F	16.4 ± 2.2b	0.0 ± 0.0	0.8 ± 0.8	17.5 ± 2.0a
	Post-treat day 21	T	256.9 ± 70.6	16.4 ± 16.4	0.0 ± 0.0	1526.8 ± 82.1
		F	13.5 ± 2.3b	0.6 ± 0.6	0.0 ± 0.0	13.8 ± 2.3a

 

Note: Prior to cabergoline treatment (pre-treatment), one female subject from the pretreated groups was assigned to dyadic encounters with one subject from the control group (C) on different days. Females were treated with cabergoline for 3 days (post-treatment); one individual encountered the same individual from the C group on day 4 and on day 21 respectively. Data are the mean±s.e.m. Means with different superscript letters vary significantly at P < 0.05 by the Wilcoxon signed-rank test.

 

Table II. Comparison of females’ investigation, aggression, defense and self-grooming and resting times (T, sec) and frequency (F) in 30 min encounters with a male counterpart between the pre-treatment and the post-treatment.

Behavioral interactions		50 µg/kg (pre- and post- treated female toward normal male)
		Pre-treated	Post- treated day 7	Pre-treated	Post- treated day 24
Investigation	T	184.8 ± 43.4	86.9 ± 24.2*	234.6 ± 45.7	183.0 ± 73.0
	F	20.0 ± 3.4	7.6 ± 1.8*	16.8 ± 2.2	14.6 ± 3.2
Aggression	T	18.8 ± 13.8	0.0 ± 0.0	0.0 ± 0.0	0.0 ± 0.0
	F	0.6 ± 0.3	0.0 ± 0.0	0.0 ± 0.0	0.0 ± 0.0
Defense	T	66.6 ± 18.7	0.0 ± 0.0*	120.8 ± 64.5	23.4 ± 13.4*
	F	8.4 ± 3.8	0.0 ± 0.0*	1.9 ± 0.8	1.0 ± 0.6
Self-grooming and resting	T	1527.0 ± 33.8	1713.1 ± 24.2*	1444.6 ± 104.0	1593.6 ± 82.5
	F	23.6 ± 2.8	7.9 ± 1.8*	18.5 ± 2.4	16.1 ± 3.7

 

Note: Prior to cabergoline treatment (pre-treatment), each female rat encountered one normal male for 30 min. Then females were treated with 50 µg/kg cabergoline for 3 days (post-treatment); one individual from post-treatment encountered the same normal male on day 7 and on day 24 respectively. Data are the mean±s.e.m. Differences between the pre-and the post-treatment group were tested using the Wilcoxon signed-rank test, * P < 0.05.

 

Table III. Comparison of females’ investigation, aggression, defense and self-grooming and resting times ( , sec) and frequency (F) in 30 min encounters with a male counterpart between the pre-treatment and the post-treatment.

Behavioral interactions		100 µg/kg (pre- and post- treated female toward normal male)
		Pre-treated	Post- treated day 7	Pre-treated	Post- treated day 24
Investigation	T	251.0 ± 58.7	178.5 ± 32.3	242.6 ± 43.3	196.7 ± 68.1
	F	19.6 ± 4.0	10.4 ± 1.6*	22.7 ± 3.3	14.6 ± 2.4
Aggression	T	0.6 ± 0.6	0.0 ± 0.0	60.1 ± 52.6	0.0 ± 0.0*
	F	0.1 ± 0.1	0.0 ± 0.0	2.7 ± 2.4	0.0 ± 0.0*
Defense	T	21.0 ± 21.0	25.3 ± 25.3	4.7 ± 2.5	0.0 ± 0.0
	F	1.3 ± 1.3	1.0 ± 1.0	0.7 ± 0.4	0.0 ± 0.0
Self-grooming and resting	T	1527.4 ± 48.6	1596.3 ± 46.8	1478.6 ± 80.5	1603.3 ± 68.1
	F	21.8 ± 3.2	11.6 ± 1.4*	25.9 ± 3.2	15.1 ± 2.5*

 

Note: Prior to cabergoline treatment (pre-treatment), each female rat encountered one normal male for 30 min. Then females were treated with 100 µg/kg cabergoline for 3 days (post-treatment), one individual from post-treatment encountered the same normal male on day 7 and on day 24 respectively. Data are the mean±s.e.m. Differences between the pre-and the post-treatment group were tested using the Wilcoxon signed-rank test, * P < 0.05.

 

P = 0.017, TableII and III). The frequency of defense toward males in the 50 µg/kg group at day 7 were lower than that in the pretreated group (Z = −2.366, P = 0.018, Table II). The frequency of self-grooming and resting decreased in treatment groups (P < 0.05, Table II and III), except for the 50 µg/kg group at day 24 (P > 0.05, Table II and III).

 

DISCUSSION

Our data showed that the PRL in female R. losea decreased in response to the 50 µg/kg cabergoline treatment at day 7 and that 50 µg/kg cabergoline treatment raised E2 secretion at day 24, which agreed with our prediction. This could be because E2 controls PRL gene expression, regulates its sensitivity, and inhibits PRL (Freeman et al., 2000; Lieberman et al., 1981; Maurer, 1982). As previously reported, E2 is antidopaminergic at the lactotroph, and its secretion increases to decrease the number of dopamine receptors (Leong et al., 1983). Thus, PRL may be released subsequently in response to dopamine receptors decreases at day 24. No direct evidence is currently available to determine whether P is an autocrine or paracrine to regulate PRL secretion (Freeman et al., 2000). In this study, P secretion of female R. losea was not influenced by 50 or 100µg/kg cabergoline. Moreover, we did not find the correlation between P and PRL in female R. losea. Our data indicated that the serum E2, P, and PRL of females treated with 100 µg/kg cabergoline were not significantly different compared with those of the control group. In general, the effects of cabergoline suppression on PRL, which is influenced by the dosage and the usage of excessively high concentration of cabergoline in a short time, may cause rapid changes in the neuroendocrine system facing challenge, pressure, hormone and/or neurotransmitter and their receptors in target organ in female R. losea. In addition, under various delivery modes and different species, the bioavailability of cabergoline was different, 30% in mice and 63% in rats (Leong et al., 1983). Therefore, further studies should be conducted that determine the appropriate dosage of cabergoline in various rodent species.

 

Our study indicated that the ovary weight of female rats treated with 50 µg/kg cabergoline at day 24 were significantly increased by 64.6% compared with those in the control group, and increased by 52.1% more than those of rats treated with 100 µg/kg cabergoline at day 24. A significant change in ovary weight may be attributed to cabergoline causing the variation of serum PRL. The neural circuitry regulating of PRL is particularly sensitive to ovarian steroids. Therefore, cell growth, migration, and differentiation in tissues are finally influenced (Beitrame et al., 1996; Freeman et al., 2000). Most uteruses of female treated with cabergoline showed that edema because the dopaminergic neurons express E2 and/or P receptors. This result is possibly induced by the regulation of Angiotensin II (ANG II) receptors (Kohama et al., 1992; Nagano and Kelly, 1994). ANG II is important in regulating blood pressure, vascular tone, and salt and water homeostasis (Warembourg et al., 1989). If this factor is one cause of the resulting uterine edema in female R. losea under cabergoline treatment, the question deserves further study. In the field, the social behaviours of a target animal may reflect its capacity for resource acquisition and social status (Benus et al., 1991; Bottari et al., 1993). Active investigative behavior between intrasexual individuals may state the social status of animals (Chen et al., 2011; Chen et al. 2017; Liu et al. 2013; Negishi and Koide, 1997; Qin et al., 2017; Wang et al. 2011). The investigation time and frequency of female R. losea toward normal females after 50 µg/kg cabergoline treatment were higher compared with that in the pretreated group, particularly in the group at day 4 after treatment. The duration of self-grooming and resting of female treated by 50 µg/kg cabergoline toward normal female decreased significantly compared with that of the pretreated group at day 4, whereas the frequency of self-grooming and resting increased within the same period. These results implied that cabergoline changed the females’ social status and tensity after treatment. However, the effect of cabergoline on the investigative behavior of female toward normal female was not observed at day 21 after treatment, which indicated the effect of cabergoline was restorable as time goes on.

Investigative behavior between intersexual individuals mainly represents amiable and sexual motivations (Cassaing and Isaac, 2007; de Boer et al., 2003). The duration and frequency of female R. losea investigation towards untreated adult males was lower in the 50 µg/kg group at day 4 compared with the untreated group. Therefore, 50 µg/kg cabergoline may change the relationship between male and female rats. Aggressive behavior in intersexual or intrasexual conspecific individuals plays an important role in social status, resources, and defense of territory throughout biology (Benus et al., 1991; Bottari et al. 1993; Liu et al., 2012; Liu et al., 2013; Wang et al. 2011). Our data showed that aggression in cabergoline-treated female R. losea is lesser than that in nontreated females and the defense behavior exhibits a similar trend. Cabergoline reduces the aggression of female R. losea toward adult males and generally may reflect that females promote amiable will and sexual motivations toward adult male.

The regulatory mechanism that cabergoline may induce the change of behavior in females was still unclear. This result is apparently regulated through the PRL and/or E2 cycle. PRL performs a significantly function in regulating the maternal behaviors of females, including cleaning, gathering, grouping, and nursing of the young (Freeman et al., 2000). Previous studies clearly indicated that the dopamine agonist bromocriptine suppresses PRL secretion and prevents the onset of maternal behavior (Spritzer et al., 2005). Moreover, E2 participates in sexual solicitation to males in mammals (Raymond et al., 1978). Thus, we infer that increase in amiable and sexual motivation behaviors in female R. losea may be attributed to E2 secretion caused by cabergoline.

 

CONCLUSION

Cabergoline does not weaken those social behaviors between intra- and inter-sexuality in female R. losea. These females still are able to keep competitive in holding vital resources and mates compared with normal females, which will contribute more effect in fertility control. Collectively, cabergoline is a potentially effective sterilant for pest rodent. Further efforts should be made to reduce costs of cabergoline bait, and explore the optimal strategy of field practice in pest rodent control.

 

Acknowledgements

This study was supported by the Natural Science Foundation of Guangdong Province (2015A030313860), Science and Technology Planning Project of Guangdong (2016A020210054) and Guangzhou (201510010018), and fund from Guangdong Academy of Sciences (2017GDASCX-0107; 2018GDASCX-0107).

 

Statement of conflict of interest

The authors declare that there is no conflict of interests regarding the publication of this article.

 

References

Amenomori, Y., Chen, C.L. and Meites, J., 1970. Serum prolactin levels in rats during different reproductive states. Endocrinology, 86: 506–510. https://doi.org/10.1210/endo-86-3-506

Bachelot, A. and Binart, N., 2007. Reproductive role of prolactin. Reproduction, 133: 361–369. https://doi.org/10.1530/REP-06-0299

Beitrame, D., Longo, M. and Mazué, G., 1996. Reproductive toxicity of cabergoline in mice, rats and rabbits. Reprod. Toxicol., 10: 471–483. https://doi.org/10.1016/S0890-6238(96)00134-7

Ben-Jonathan, N., Lapensee, C.R. and Lapensee, E.W., 2008. What can we learn from rodents about prolactin in humans? Endocrinol. Rev., 29: 1–41. https://doi.org/10.1210/er.2007-0017

Benus, R.F., Bohus, B., Koolhaas, J.M. and Van Oortmerssen, G.A., 1991. Heritable variation for aggression as a reflection of individual coping strategies. Experientia, 47: 1008–1019. https://doi.org/10.1007/BF01923336

Bottari, S.P., De Gasparo, M., Steckelings, U.M. and Levens, N.R., 1993. Angiotensin II receptor subtypes: Characterization, signalling mechanisms, and possible physiological implications. Front. Neuroendocrinol, 14: 123–171. https://doi.org/10.1006/frne.1993.1005

Brown, P.R., Douangboupha, B., Htwe, N.M., Jacob, J., Mulungu, L., Phung, N.T.M., Singleton, G.R., Stuart, A.M. and Sudarmaji, 2017. Control of rodent pests in rice cultivation. In: Achieving sustainable rice cultivation (ed. T. Sasaki), Burleigh Dodds Science Publishing, Cambridge, UK. pp. 1–34. https://doi.org/10.19103/AS.2016.0003.24

Buckle, A.P. and Smith, R.H., 2015. Rodent pests and their control. 2nd Edition. CAB International: Oxford, UK. https://doi.org/10.1079/9781845938178.0000

Cassaing, J. and Isaac, F., 2007. Pair bonding in the wild mouse Mus spretus: Inference on the mating system. C.R. Biol., 330: 828–836. https://doi.org/10.1016/j.crvi.2007.07.008

Caughley, G., Pech, R. and Grice, D., 1992. Effect of fertility control on a population’s productivity. Wildl. Res., 19: 623–627. https://doi.org/10.1071/WR9920623

Chen, Q., Liu, Q.S., Qin, J., Guo, M.F., Wang, D. and Shi, D.Z., 2011. Mating system of lesser rice-field rat Rattus losea: the effects of familiarity on intersexual interaction. Sichuan J. Zool., 30: 845–849.

Chen, Y., Su, Q.Q. and Liu, Q.S., 2017. Effects of quinestrol on the vocal behavior of mice during courtship interactions. Physiol. Behav., 173: 216–222. https://doi.org/10.1016/j.physbeh.2017.02.017

De Bore, S.F., Van Der Vegt, B.J. and Koolhaas, J.M., 2003. Indi­vidual variation in aggression of feral rodent strains: a standard for the genetics of aggression and violence? Behav. Genet., 30: 485–501. https://doi.org/10.1023/A:1025766415159

Ericsson, R.J., 1970. Male antifertility compounds: U-5897 as a rat chemosterilant. J. Reprod. Fertil., 22: 213–222. https://doi.org/10.1530/jrf.0.0220213

Ferraro, F., Nisoli, L.G.C., Salvo, R., Maffeo, G. and Jöchle, W., 1995. Periodic use of cabergoline, a prolactin inhibitor, for control of reproductive success in rats: work in progress. Theriogenology, 44: 1–7. https://doi.org/10.1152/physrev.2000.80.4.1523

Freeman, M.E., Kanyicska, B., Lerant, A. and Nagy, G., 2000. Prolactin: structure, function, and regulation of secretion. Physiol. Rev., 80: 1524–1585.

Guo, Z.N., Su, C.H., Chen, G.W. and Zheng, Z.M., 2014. Study on population age determination of Rattus losea. Chin. J. Hyg. Insect Equip., 20: 332–325 (in Chinese).

Hearn, C.M., Shaw, G., Short, R.V. and Renfree, M.B., 1998. Effects of cabergoline on reproduction in three families of Australian marsupials. J. Reprod. Fertil., 113: 151–157. https://doi.org/10.1530/jrf.0.1130151

Jöchle, W., Arbeiter, K., Post, K., Ballabio, R. and Dver, A.S., 1989. Effects on pseudopregnancy, pregnancy and interoestrous intervals of pharmacological suppression of prolactin secretion in female dogs and cats. J. Reprod. Fertil., Suppl. 39: 199–207.

Kohama, S.G., Freesh, F. and Bethea, C.L., 1992. Immunocytochemical colocalization of hypothalamic progestin receptors and tyrosine hydroxylase in steroid-treated monkeys. Endocrinology, 131: 509–517. https://doi.org/10.1210/endo.131.1.1351839

Krebs, C.J., 2014. Rodent biology and management. Integr. Zool., 9:229–230. https://doi.org/10.1111/1749-4877.12090

Leong, D.A., Frawley, L.S. and Neill, J.D., 1983. Neuroendocrine control of prolactin secretion. Annu. Rev. Physiol., 45: 109–127. https://doi.org/10.1146/annurev.ph.45.030183.000545

Li, Z.L., Zhou, H.F., Zhou, B.R., Liu, B., Jiang, X. F. and Xu, J.Y., 2019. Effect of a traditional Chinese medicine formula (Bu Shen Zhu Yun) on mifepristone-induced abnormal pituitary gonadotropin secretion in rats. Pakistan J. Zool., 51: 643-653. http://dx.doi.org/10.17582/journal.pjz/2019.51.2.643.653

Lieberman, M.E., Maurer, R.A., Claude, P., Wiklund, J., Wertz, N. and Gorski, J., 1981. Regulation of pituitary growth and prolactin gene expression by estrogen. Adv. exp. Med. Biol., 138: 151–163. https://doi.org/10.1007/978-1-4615-7192-6_9

Liu, M., Qu, J.P., Wang, Z.L., Wang, Y.L., Zhang, Y.M. and Zhang, Z.B., 2012. Behavioral mechanisms of male sterilization on plateau pika in the Qinghai-Tibet plateau. Behav. Process., 89: 278–285. https://doi.org/10.1016/j.beproc.2011.12.009

Liu, Q.S., Feng, Z.Y., Gong, P.B., Qin, J., Gao, Z.X., Huang, X.L., Yao, D.D. and Yan, S.X., 2010. Effects of high-fiber food on food intake and digestibility in the lesser rice-field rat (Rattus losea). Acta Theriol. Sin., 30: 291–296 (in Chinese).

Liu, Q.S., Qin, J., Chen, Q., Wang, D. and Shi, D.Z., 2013. Fertility control of Rattus nitidus using quinestrol: effects on reproductive organs and social behavior. Integr. Zool., Suppl. 1: 9–17. https://doi.org/10.1111/j.1749-4877.2012.00296.x

Lv, X.H. and Shi, D.Z., 2011. Effects of levonorgestrel on reproductive hormone levels and their receptor expression in Mongolian gerbils (Meriones unguiculatus). Exp. Anim., 60: 363–371. https://doi.org/10.1538/expanim.60.363

Marks, C.A., Jalkanen, L., Savolainen, R. and Short, R.V., 2001. Control of red fox (Vulpes vulpes) fertility with cabergoline: dose response and timing of intervention. Reproduction, 122: 147–154. https://doi.org/10.1530/rep.0.1220147

Maurer, R.A., 1982. Estradiol regulates the transcription of the prolactin gene. J. biol. Chem., 257: 2133–2136.

Mednick, D.L., Barkley, M.S. and Geschwind, I.I., 1980. Regulation of progesterone secretion by LH and prolactin during the first half of pregnancy in the mouse. J. Reprod. Fertil., 60: 201–207. https://doi.org/10.1530/jrf.0.0600201

Munawar, N., Hussain, I. and Mahmood, T., 2018. Occurrence of rodent species in agricultural lands during cropping and non-cropping seasons of Pothwar Plateau, Pakistan. Pakistan J. Zool., 50: 1663–1669. https://dx.doi.org/10.17582/journal.pjz/2018.50.5.1663.1669

Nagano, M. and Kelly, P.A., 1994. Tissue distribution and regulation of rat prolactin receptor gene expression. Quantitative analysis by polymerase chain reaction. J. biol. Chem., 269: 13337–13345.

Negishi, H. and Koide, S.S., 1997. Prevention and termination of pregnancy in rats by cabergoline, a dopamine agonist. J. Reprod. Fertil., 109: 103–107 https://doi.org/10.1530/jrf.0.1090103.

Post, K., Evans, L.E. and Jöchle, W., 1988. Effects of prolactin suppression with cabergoline on the pregnancy of the bitch. Theriogenology, 29: 1233–1243. https://doi.org/10.1016/0093-691X(88)90003-9

Prakash, I., 1988. Rodent pest management. CRC Press, Boca Raton, Florida.

Qin, J., Su, Q.Q. and Liu, Q.S., 2015a. Effects of cabergoline on germ cells and enzymes in testis of male Rattus losea. Acta Theriol. Sin., 35: 184–189(in Chinese).

Qin, J., Su, Q.Q. and Liu, Q.S., 2017. The effects of cabergoline on social behavior in male Rattus losea. Acta Theriol. Sin., 37: 277–283(in Chinese).

Qin, J., Su, Q.Q., Wang, D., Shi, D.Z., Cao, Y.S. and Liu, Q.S., 2015b. Cabergoline reduces serum LH and sperm quality of male Rattus losea. Pakistan J. Zool., 47: 831–838.

Raymond, V., Beaulieu, M., Labrie, F. and Boissier, J., 1978. Potent antidopaminergic activity of estradiol at the pituitary level on prolactin release. Science, 200: 1173–1175. https://doi.org/10.1126/science.418505

Shi, D.Z., Wan, X.R., Davis, S.A., Pech, R.P. and Zhang, Z.B, 2002. Simulation of lethal control and fertility control in a demographic model for Brandt’s vole (Microtus brandti). J. appl. Ecol., 39: 337–348. https://doi.org/10.1046/j.1365-2664.2002.00716.x

Singleton, G.R., Hinds, L.A., Leirs, H. and Zhang, Z. (Eds), 1999. Ecologically-based management of rodent pests. Australian Centre for International Agricultural Research: Canberra.

Spritzer, M.D., Meikle, D.B. and Solomon, N.G., 2005. Female choice based on male spatial ability and aggressiveness among meadow voles. Anim. Behav., 69: 1121–1130. https://doi.org/10.1016/j.anbehav.2004.06.033

Su, Q.Q., Xiang, Z.F., Qin, J. and Liu, Q.S., 2013. Effects of cabergoline in lactating mice on survival and body growth of their pups. Acta Theriol. Sin., 33: 361–366(in Chinese).

Su, Q.Q., Xiang, Z.F., Qin, J. and Liu, Q.S., 2014. Effects of cabergoline on the fertility of female mice during early and late pregnancy and potential for its use in mouse control. Crop Prot., 56: 69–73. https://doi.org/10.1016/j.cropro.2013.10.025

Wang, D.W., Li, N., Liu, M., Huang, B.H., Liu, Q. and Liu, X.H., 2011. Behavioral evaluation of quinestrol as a sterilant in male Brandt’s voles. Physiol. Behav., 104: 1024–1030. https://doi.org/10.1016/j.physbeh.2011.06.024

Wang, D.W., Zhang, J.X., Wang, Z.L. and Zhang, Z.B., 2006. Seasonal changes in chronic social interactions and phys­iological states in female rat-like hamsters (Tscheskia triton). Physiol. Behav., 89: 420–427. https://doi.org/10.1016/j.physbeh.2006.07.006

Wang, J.S., Feng, Z.Y., Yao, D.D., Sui, J.J., Zhong, W.Q., Li, M. and Dai, J.Y., 2008. Warfarin Resistance in Rattus losea in Guangdong Province, China. Pestic. Biochem. Physiol., 91: 90–95. https://doi.org/10.1016/j.pestbp.2008.01.007

Warembourg, M., Jolivet, A. and Milgrom, E., 1989. Immunohistochemical evidence of the presence of estrogen and progesterone receptors in the same neurons of the guinea pig hypothalamus and preoptic area. Brain Res., 480: 1–15. https://doi.org/10.1016/0006-8993(89)91561-8

Yang, H.Y., Feng, Z.Y., Lu, R.M., Zhang, T., Liu, M.Q., Zhang, S.Y., Mai, H., Liang, Q.G. and Liang, L., 2006. Study on character of plague focuses in Guangdong province. J. trop. Med., 6: 794–807(in Chinese).

Zhang, Z.B., 2000. Mathematical models of wildlife management by contraception. Ecol. Model., 132: 105–113. https://doi.org/10.1016/S0304-3800(00)00308-2

Zhang, Z.B. and Wang, Z.W., 1998. Ecology and management of rodent pests in agriculture. Ocean Press, Beijing, pp. 175–191 (in Chinese).