Effect of oxytocin on maternal aggression behavior in rat stress model
ã€Abstract】 Objective To investigate the effects of different doses of oxytocin on the aggression behavior of Wistar pregnant rats. Methods Forty pregnant rats were divided into experimental group (A, B, C) and control group (D) according to the random number table, 10 in each group. Among them, A, B and C groups were forced to swim before each stress. Administered by the abdominal cavity o. 3 mg/kg, 1.0 rag/kg, 2.0 mg/kg oxytocin, and group D received an equal volume of normal saline. On the 3rd day of each group, the maternal aggression behavior test was carried out. The main attack, the number of bites, the number of times of climbing, the attack latency and the duration of the attack were observed. The differences in attack behavior between the groups were compared and the elevated cross was used. The maze was used to analyze and compare the data of the open arms and the closed arms of each group of rats. Results There was a statistically significant difference in the duration of attack and latency between group A and group D [(147.60+23.92)s, (79.70_+9.88)s, P<0.05], other items. There was no statistical difference (P>0.05); there were statistically significant differences between group B and group D except the total number of attacks (P>0.05) (3.10_+0,87) times, (13 .60_+5.14) times, (91.30+9.74)s, (167.20_+30.02)s, P
[Key words] stress model; anxiety; oxytocin; maternal aggression; elevated cross maze
Stress, also known as stress response, is widespread in all organisms. Experimental and clinical studies have confirmed that stress can induce a variety of behavioral changes, such as anxiety, depression, escape/aggressive behavior abnormalities, etc. In addition, stress can also activate the neuroendocrine system, which in turn causes a significant increase in glucocorticoids and catecholamine levels. A small increase in oxytocin. Oxytocin (OXT), also known as oxytocin, is a nonapeptide neuroendocrine hormone synthesized by the supraoptic nucleus and paraventricular nucleus cells and passes through the hypothalamus. pituitary. The gonadal axis acts on the central nervous system and the peripheral nervous system. In addition to the most common promotion of uterine contraction and lactation, the latest domestic and international research has also found that it has socializing, maternal behavior, anti-stress, and oxytocin in pregnant women. The content of the hormone has a great correlation with the intimacy of the children. Therefore, foreign scholars also call it "intimate hormones". Maternal aggression (MA) is another complex behavioral term after the study of stepmother's love behavior at home and abroad in recent years. It refers to rodents playing to protect potential infants from threats to young invaders. A protective behavioral response is closely related to maternal behavior. According to the study, MA is related to stress response and is mainly regulated by oxytocin in the body, thus maintaining the stable and healthy development of the population. In this experiment, a pregnant rat stress model was established by forced swimming to study the changes of MA, and it was investigated whether it could protect MA by anti-stress by injecting different doses of oxytocin.
Materials and Methods
First, the material
1. Laboratory animals and medicines: 40 healthy and clean Wistar pregnant rats, body weight (260+30) g, provided by Dalian Medical University Experimental Animal Center, certificate number: SCXK (Liao) 2008-0002, standard environment breeding. According to the random number table, 40 pregnant rats were randomly divided into four groups of A, B, C and D, with 10 in each group. Twenty sexually mature males, weighing (250 + _25) g, as human invading rats. Dedicated Wistar rat oxytocin injection, o. 9% saline was provided by the Behavioral Laboratory of the Life Science Center of Jiamusi University.
2. Experimental instrument (provided by Shanghai Xinsoft Information Technology Co., Ltd.): (1) Forced swimming tube: cylindrical shape 30 cm x 50 cm (diameter × height), water depth 40 cm. (2) Attack behavior experiment box: the specification is 61 cmx 4lcmX51 cm, and the upper part is covered with two transparent glass plates, and the inside is evenly covered with a layer of dry wood chips of about l ctn thick. (3) Overhead f-maze: consisting of a -x inch open arm (50 cmX10 cm), a pair of closed arms (50 cm x 10 cm x 40 cm) and a central zone (10 cm x 10 cm). The labyrinth is 50 cm from the ground. The bottom of the labyrinth and the wall of the closed arm are made of black plastic panels.
Second, the method
1. Modeling: Refer to the classic forced swimming modeling method. During the period from the 14th day of pregnancy to the day of delivery, the rats of group A, B and C were intraperitoneally injected with 0.3 rag/kg, 1.0 111, 7 kg and 2.0 mg/kg oxytocin before the model was established. Group D was given an equal volume of physiological saline. After 10 minutes of injection, the rats were placed in a forced swimming tube with a set temperature (19-21 °C) for 10 minutes. After each swim, they were wiped dry and placed directly in the dry cage.
2. Behavioral testing (1) Maternal aggression behavior experiment: Under quiet natural light, put the mother and the cub into the attack behavior experiment box to adapt to 2 nlin before each experiment, then put the invading mouse into the box and start the video. Shoot 10 rain. The observed indicators are as follows: total number of attacks, attack latency, duration of attacks, number of bites, and number of times of climbing. (2) elevated cross maze experiment: in a quiet and dark room, first open the labyrinth l: incandescent light at 100 cm; put the mother into the experimental box for 5 min, then put the maze specified position to detect 5 nlin ( Waiting for the mouse to open the shooting system 10 s before the labyrinth officially began to detect). Observed indicators have general indicators and related exploration. Risk assessment indicator. The former mainly has the open arm entry (OE), the open arm time (OT), the number of closed arms (C|ose arnl entry, CE), and the closed arm time (CT). ), OE percentage, OT percentage. The latter mainly has head dipping (HD), rear-rear leg (relation, RE), and stretch-attend postures (SAP).
3. Statistical methods: Count data were expressed as mean ± standard deviation. The experimental data were tested for variance homogeneity and one-way ANOVA using SPSS 17.0 statistical software. LSD was used for comparison between groups. t test and SNK-q test. P<0.05 was considered as the difference.
Discussion <br>Experimental studies on aggression have been reported, but the data are not completely consistent, which may be related to a variety of factors such as rat population, stimulation intensity and time, mode of administration, precision of testing equipment. In this study, the classical stress model was replicated by forced swimming, and then intervened by oxytocin (OXT), so that the abnormal maternal aggression behavior (MA) after induction of stress tends to normalize or reduce its stress symptoms and promote the development of MA. .
In the MA experiment, it was observed that the saline control group decreased in different degrees of bite, number of times of climbing, total number of attacks, and attack latency, indicating that stress would destroy the ability of the mother to repel the invading mouse (in the experiment) It can be seen that the invaders are slow to respond when the rats are pressed, which is consistent with previous literature reports. However, after different doses of OXT, the stress status is improved to some extent, which is consistent with the existing reports. However, as for the increase in the total number of attacks or the increase in the number of bites, there is no final conclusion, and there are reports of an increase in the number of chases. This shows that there is a lack of standards for measuring the quality of attacks. In addition, in the saline group, chyme occurred during the experiment, which directly led to a sharp decline in the number of guinea pigs, which in turn affected the olfactory response and alert response of the mother, which greatly reduced the protective ability of the larvae, while the intervention group was effective. The reduction of chyme is rarely mentioned in previous reports, which may be related to the role of OXT in social relations (enhancing mutual trust and intimacy). This study found that there were statistically significant differences in the number of bites, duration of attack, and attack latency between groups A, B, and C, indicating that OXT may have a dose-dependent effect on MA protection after stress; Whether the OXT dose can continue to increase, need to consider the toxicological significance (OXT side effects are mainly elevated blood pressure, pulse speed, water retention, etc.), domestic and foreign literature also mentioned very little in rodent research. In fact, maternal love behavior is also accompanied by MA, thus ensuring the survival rate of the pups and the continuity of the species.
By EPM, the percentage of OT and OE in group D were significantly lower than that in group A, and the time to enter the closed arm (CT) was also significantly prolonged, indicating that OXT may increase the effect of stress rats on the open arms. The further injection of OXT (especially group B) found that the percentage of OT, OE, OT, and OE increased significantly, indicating that OXT has certain anti-anxiety and anti-stress effects and dose compliance, which may also be related to MA and forced swimming. The above-mentioned effects are exerted by the increased release of OXT-induced amino acids (such as GABA and glutamate) or by inhibition of the combination of corticotropin releasing factor (CRF) and corresponding receptor 2 (CRFR.2), while the latter It is considered to be one of the important factors for OXT to exert anxiety and adapt to the stressful environment. In addition, there are also reports in the literature, pituitary vasopressin (AVP), estrogen receptor and testosterone, 5. Hormone proteins such as HT and dopamine and corresponding brain nuclei (such as nucleus accumbens, hippocampus) may also be involved in the anti-stress physiological effects of OXT. Compared with the B and C groups, the improvement of the experimental index of the A group is small, but there are still differences, which may be related to the short half-life of OXT in plasma (about 3-10rain). In addition, according to Alica et al. Developed EPM usage specifications, EPM can also detect and evaluate and explore. The number of hazard-related indicators, namely HD, RE, and SAP, more fully reflects the activity of the rat in the open arms, the closed arms, the central region, the risk (such as MA in this experiment), and the degree of stress. It has been confirmed in domestic and foreign literature. The number of HD, RE and SAP in group D was significantly lower than that in group c, and HD was significantly lower than that in group A. The difference between RE, SAP and group B was significant, indicating that the degree of anxiety stress in stress rats was not only blind to m-JI in open arms. The proportion of q times is related, and there is a correlation between exploring and coping with dangerous behaviors, which is well reflected in MA.
In short, the stress response caused by forced swimming will destroy the intrinsic components of the maternal behavior of the mother after childbirth, namely the maternal love behavior (such as the establishment of acupoints, clams, clams, combing hair, n-milk behaviors) and MA, And for MA's behavioral changes or physiological psychological impact (inducing anxiety, depression, ulcerative bleeding, etc.) is greater, which is consistent with foreign literature reports. By giving different doses of OXT, it can effectively interfere with the behavior or behavioral compensation. The mechanism of OXT protection against MA is still unclear, and further research is needed from molecular, genetic, and psychological aspects. The experiment did find that the maternal and child intimacy increased, which may be the prospect of OXT treatment, which can ensure the survival rate of the population. Therefore, it is necessary to give a large amount of basic and clinical experimental data to determine whether it is possible to give other species that are not harmonious with mother and child so that humans have certain OXT.
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