ARTICLE INFO

Article Type

Original Research

Authors

Hamidi   Gh.A. (1)
Salami   M. (1)
Talaei   S.A. (*)






(*) Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran
(1) Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran

Correspondence

Address: Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran
Phone: 0098 913 362 3240
Fax: 0098 31 5562 1157
talaei@kaums.ac.ir

Article History

Received:  February  24, 2018
Accepted:  September 22, 2018
ePublished:  October 10, 2018

BRIEF TEXT


Maternal deprivation is one of the stressors that affects children in their early stage of lives leading to cognitive and neurochemical impairments in the brain [1].

Maternal deprivation although can reduce spatial learning in the rats’ offsprings, but it has no effect on the consolidation of spatial memory [2]. On the other hand, maternal deprivation enhances spatial learning [3]. ... [4, 5]. Maternal deprivation increases the activity of the HPA axis and producing cortisol in children, which results in increased risk behaviors [6]. ... [7-10]. Modification of learning and memory processes by morphine and other opioids has been studied in several studies resulting in contradictory results [11-15].

The aim of this study was to investigate the effects of maternal deprivation on spatial learning and memory of morphine-dependent rats.

This research is an experimental study.

This study was conducted on male Wistar rats in Kashan.

This experimental study was performed on 40 male Wistar rats (45 days old) ranging weighting 120 to 140 g.

Animals were kept at the animal breeding center of Kashan University of Medical Sciences at 22±2°C, 55±5% humidity and 12:12 h light-darkness cycle; 12 h of light started at 7 pm. Experiments on animals were in accordance with the Ethics Committee of the Vice-Chancellor of Research of Kashan University of Medical Sciences. Rats were randomly assigned into 5 groups (n=8) as follows: Control (CO), and Morphine dependent (MD), and maternal separation for one week (MS1), 2 weeks (MS2) and 3 weeks after birth (MS3) groups. In maternal separation groups [2], the female rat was brought out every day at 10 and was returned to the cage at 13, during which the infant’s cage was placed in a chamber at 35 to 37°C. Breastfeeding stopped for all animals on 22nd day after birth. 45 days after birth, at which based on several studies, After reaching, based on the report of many studies of rats have fully matured brain [17, 16], all animals except for the control group, for 10 days every 12 h, received (ip) morphine sulfate (10 mg/Kg) subcutaneously. On the 10th day, symptoms of morphine deprivation syndrome were evaluated as follows: Two h after receiving morphine, 2 mg/kg of naloxone hydrochloride (Toliddaru, Iran) was injected intraperitoneally into animals and immediately transferred to a plexiglass chamber with a diameter of 30 and height of 50 cm. The deprivation symptoms were assessed and evaluated based on the modified Gellert-Holtzman model [18] for 30 min. From the next day, learning and spatial memory of rats using Morris water maze were investigated for four consecutive nights [19]. The behavior of the animal in the maze is monitored through a monitored camera and analyzed by the digital tracking system (Version 7.1). The acquisition step was carried out as follows: the animal was released to the water from one of the four hypothetical positions facing the maze wall and allowed for swimming for a maximum of 60 s in the maze. The rat begins to swim in water after being released. If the animal accidentally found the hidden platform, it was allowed to stay on the platform for 15 s and identify the location around it. If within 90 s the rat could not find the platform, the researcher would guide the animal steadily to the platform until the rat found the platform. The rat was then removed from the platform and returned to its cage after drying with a towel. The experiment was repeated 10 min later; however, the rat was released from different location. Each rat experienced 4 experiments with 10 min intervals daily. Through the sessions of the experiments, the spent time and traveled distance by the rats to find the platform reduced. The number of sessions at this stage was 16 sessions, which lasted 4 consecutive days. After completing this step, the probe trial was performed [20]. The data obtained from learning test was analyzed by Repeated measure ANOVA and other results were assessed by one-way ANOVA and Bonferroni post-hoc test.

Receiving morphine by rats induces their dependence and they showed symptoms of morphine deprivation. According to the Gellert-Holtzman score, there was a significant difference between two groups (p<0.0001). There was a direct correlation the severity of the symptoms of deprivation syndrome and the levels of deprivation. The relationship between from the maternal treatment was related. The post-test results showed a significant difference between MS2, MS3 and MD groups (P<0.001, Fig. 1). The spent time and distance traveled factors to find the hidden platform are used as the criterion for spatial learning of animals. Learning occurred in all groups within 4 days of study for all animals (p<0.0001); according to Figure 2, through the test, animals of different groups spent less time and less distance to find the hidden platform in the maze. Also, there was a significant difference between the learning process between different groups (p<0.0001). Bonferroni post-hoc test results showed that the dependence of rats on morphine did not affect the spent time and distance traveled in the maze to find the hidden platform in comparison with the CO group (p>0.05 for both comparisons). Moreover, according to Figure 2, maternal deprivation for 3 weeks caused male baby rats to spend more time and longer distance to find the hidden platform in the maze (comparison between CO and MS3; p<0.01). There was a significant difference between the different study groups in the spent time and distance traveled in each quadrant of Morris water maze (P<0.001). According to Figure 3, morphine did not alter the level of spatial memory consolidation in rats; in other words, there was no significant difference between CO and MD groups in each quadrant of Morris water maze (P>0.05 for both comparisons). Maternal deprivation in the breastfeeding period in a time-dependent manner reduced the spent time and the traveled distance in each quadrant of Morris water maze by rats, so that the following values obtained for MS3 group: 4.64±1.87 s and 229.68±41.58 cm (Fig. 3). Bonferroni post-hoc test results indicated a significant difference between the mean spent time and traveled distance in each quadrant of Morris water maze by rats in the CO and the MS2 and MS3 groups (p<0.001 for all four comparisons).

It has been shown that maternal deprivation, even short-time, both in human samples and animal models, is a stressful factor, leading to impairment in cognitive and neurochemical activities [1]. ... [22-31]. Maternal deprivation has been shown to reduce BDNF protein expression (a protein that plays a key role in the health and vitality of the neurons), and NR2A and NR2B subunits of the NMDA receptor in the hippocampal region [5]. Sousa et al. stated that maternal deprivation through the 2nd to 4th days after birth caused plasma corticosterone levels in 70 weeks old rats to be significantly higher than that of the control group. It also impaired synaptic placticity of the CA1 region neurons in the hippocampus [32].

None declared.

None declared.

Maternal separation impairs spatial learning and memory in rats.

We thank all who helped us in this study, especially Ms. Mozhgan Mohammadifar, Fatemeh Aghighi, Seyyed Mehdi Jalali and Hossein Assari.

None declared.

None declared.

This study (Study ID. 96159) was funded by the Vice-Chancellor for Research and Technology of Kashan University of Medical Sciences.

TABLES and CHARTS

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