Effect of chronic stress and intra-amygdal memantine administration on alterations of brain's volume and weight to volume and weight ratio of the adrenal gland in male mice

Background and Objective: After chronic stress, brain volume and weight reduces and in turn, adrenal weight and volume increases. This study was performed to determine the effect of chronic stress and memantine administration within amygdala on the alterations of brain's volume and weight ratio to volume and weight of the adrenal gland on male mice

Methods: In this experimental study, bi- or unilateral amygdala cannulation was preformed stereotaxically. A week after recovery, animals were received different doses of memantine [1, 0.5, and 0.1 microg/mouse], five min before stress induction. Electric foot shock induced to animals for seven consecutive days. At the end of the seventh day, animals were sacrificed and their brain and adrenal glands were fixed in formalin 4%. The volume and weight was determined by mercury immersion and accurate balance respectively

Results: Stress non- significantly reduced brain's volume ratio to volume of the adrenal gland and brain's weight ratio to weight of the adrenal gland. Memantine administration within amygdala inhibited stress effect. Memantine administration in low and medium doses within right and left amygdala significantly increased brain's volume and weight ratio to volume and weight of the adrenal gland [P<0.05]

Conclusion: Memantine dose and side dependently inhibits the effect of induced stress in male mice. Also, unilateral memantine administration within the left and right amygdala was more effective

[Effect of oral morphine consumption on the development of prosencephslon and rhombencephal brain vesicles in rat embryos]

Previous studies have shown that morphine consumption during pregnancy may delay the embryo development and/or cause abnormal nervous system function. The present study focused on the effects of maternal morphine consumption on the brain vesicles Prosencephslon and Rhombencephal development in Wistar rat embryos. A total of 12 female Wistar rats [170-200g] were used in this study. After pregnancy, each rat in the experimental group [n= 6] received 0.05 mg/ml of morphine by tap water, while the animals in the control group only received water only. On the 10th day of pregnancy, the pregnant animals were anesthetized by chloroform and the embryos were removed surgically. The embryos were then fixed in 10%formalin for one week, followed by tissue processing, sectioning, and staining with hematoxylin and eosin [H and E] for each embryo. The sections were examined for primary brain Rhombencephal and Prosencephslon vesicles, and the brain layer development or thickness was examined by light microscopy and MOTIC software. A severe reduction of the area for Rhombencephal and Prosencephslon was observed in the experimental group compared with the control group. Furthermore, the increase in the brain layer thickness was significantly more apparent in the experimental groups in comparison to the control group [P<0.05]. Our results show that oral morphine consumption causes a decrease in the primary brain vesicles. This defect may be the cause of abnormal central neuron system function and development observed in the fetuses born from opioid addicted women

[Effect of oral morphine consumption on lacunas development in ten day placenta pregnant wistar rats]

Previous studies indicated that morphine consumption during pregnancy could inhibit embryos development. Present study further evaluated the effects of oral morphine consumption on the placenta lacunas development in ten day pregnant Wistar rats. Female Wistar rats [W: 170-200 gr] were used in the present study. Experimental group were received morphine [0.05 mg/ml of tap water] after one night coupling with male rats for mating. On the day 10th of pregnancy, the pregnant animals were killed with chloroform and the placentas and uterus were removed surgically and fixed in 10% formalin for twenty days. The fixed placentas were processed and stained by H and E method and evaluated for their development. Thickness of layers, surface area of lacuna, as well as the number of cells in both maternal and fetal parts of the placentas was assessed by light microscopy. Our results indicated that the layer thickness of fetal portion and surface area of lacuna of the fetal and maternal portion of placenta reduced in experimental group. In addition, maternal portion layer thickness and cell number of the fetal and maternal portion of placenta increased in the experimental group. Our results showed that oral morphine consumption could inhibit natural function of placenta lacuna and fetal cell development

Effect of aqueous extract of trigonella foenum-graecum on pain and inflammation induced by formalin in male mice

Studies have emphasized the effect of Trigonella foenum-graecum extract on the reduction of pain and inflammation. In this research we investigated the mechanisms of Trigonella foenum-graecum extract in reducing pain and inflammation induced by formalin. Male Albino mice [weight 20 - 25 g] were evaluated through the injection of 2 microliters of formalin to the plantar part of right foot. Following this, the rate of animal foot pain and inflammation were measured using Dubbison-Dennis and immersion in mercury. Trigonella foenum-graecum extract was injected 30 minutes before administration of formalin to the animals intraperitoneally. In addition, blood samples were taken from animals and corticosterone concentrations were measured. In an in vitro study the effect of extract on the activity of cyclooxygenase type 1 and 2 was assessed. Our results showed that Trigonella foenum-graecum extract inhibits the first and second phase of pain induced by formalin, while inflammation is slightly reduced. Also the effect of Trigonella foenum-graecum extract is reversible with naloxone or memantine administration. Also Trigonella foenum-graecum extract could not increase plasma corticosterone level and was ineffective in activity of cyclooxygenase type 1 and 2 enzyme. Although Trigonella foenum-graecum extract can inhibit pain induced by formalin administration, but it seems that the reduction of pain is due to the possible interaction of components of Trigonella foenum-graecum extract with opioid and/or glutamate systems which occurs in the body and the mechanisms of inflammation reduction are not activated by the extract

[ effect of oral morphine consumption on choroid plexus and 4[th] ventricle development in embryos of 14-day wistar rats]

Previous studies have shown that morphine consumption during pregnancy may delay embryo development or cause the nervous system to function abnormally. The present study focused on the effects of maternal morphine consumption on fourth ventricle and choroid plexus development in Wistar rats. Wistar rats weighing between 170 and 200 grams were selected for this study. The experimental group after pregnancy received 0.05mg/ml of morphine in their drinking water daily. The control group received only tap water. On day fourteen of pregnancy, the pregnant animals were anesthetized by chloroform and the embryos were removed surgically. The embryos were fixed in 10% formalin for 4 weeks. Then, tissue processing, sectioning and staining hematoxylin and eosin [HandE] were applied on the embryos. The sections were examined for fourth ventricle and choroid plexus development by light microscope and MOTIC software. The results of the study indicated the choroid plexus area in the experimental group increased. Moreover, the fourth ventricle area reduction in the experimental group was significant in comparison with that in control group. This study showed that oral morphine consumption has can decrease the fourth ventricle and increase choroid plexus area. This defect may delay the functioning and development of central neuron system. such as, changes observed in the fetus born by opioid addicted women

[ effect of tea [Camellia thea Lk.] on acceleration of acetaminophen's effectiveness in headache]

Headache is the most common complaint in patients. In order to alleviate the headache, specialists have recommended different chemical and non-chemical drugs. Acetaminophen is one of the widespread analgesic drugs used for headache relief. On the other hand, tea [Camellia thea Lk.] is the most common drink for the most people world wide. In addition, previous studies indicated that tea's alkaloids seem to inhibit the acetaminophen metabolism. The present study aims to assess the effect of tea consumption on effectiveness of acetaminophen. In order to test the hypothesis, 120 patients suffered from headache referred to the Shaheed Motahari general hospital in Jahrom [Fars province, south of IRAN] were requested to take part in a single blind clinical trial study. 58 patients as the case group have received a glass of tea and after 20 min they had taken a 325 mg acetaminophen tablet. 62 patients as the control group received a glass of warm water and 20 min later had the same drug. Pain intensity was twice measured by a self-report questionnaire. The first one was 15 min before the tea or water consumption and the second, 60 min after receiving the acetaminophen. Results showed that: consumption of tea before taking acetaminophen significantly reduced the pain intensity comparing with the control group. In addition, with respect to sex and age, no significant differences were found between the groups. It can be concluded that consumption of tea before taking acetaminophen may accelerate the analgesic effectiveness of the drug

Effects of the Crocus sativus L. extract on the acquisition and expression of morphine-induced conditioned place preference in female mice

Experiments indicated that Crocus sativus L. extract may have an interaction with morphine. The effects of C. sativus on the euphoric properties of morphine in female mice did not studied. In the present study, the effects of water extract of C. sativus stigma on the acquisition and expression of morphine-induced conditioned place preference [CPP] in female N-MARI mice [20-25 g] were investigated. This experimental study was conducted on the 136 female mice that were divided in 17 groups [n=8/group]. In a pilot study, different doses of morphine [1, 10 and 20 mg/kg] and the extract [10, 50 and 100 mg/kg] were injected to the animals for evaluation of the drugs ability to induction of place preference. In the second phase of the experiments, the extract of the C. sativus was administered during or after induction of morphine CPP. Then, CPP were tested in the animals. One-way Analysis of Variance [ANOVA] was proformed for statistical procedure. Administration of morphine [1, 10 and 20 mg/kg], increased the time spend in the compartment paired with morphine [i.e. conditioned place preference-CPP]. The increament was significant for the dose 10 and 20 mg/kg of morphine. Administration of the plant extract [50 mg/kg] also produced a significant CPP. Injection of the same doses of the extract before morphine [10 mg/kg] administration, caused a decrease in the time spent in drug-paired side in doses 50 and 100 mg/kg of the extract. In addition, injection of the plant extract in the test day to the animals in which received morphine [10 mg/kg] in the conditioning days decreased the expression of morphine CPP in the animals which was statisticaly significant for dose 10 mg/kg of the extract. It could be concluded that injection of the extract of C. sativus can inhibit the acquisition and expression of morphine-induced CPP. In addition, the extract produced CPP in female mice by it-self. These results indicated that saffron extract might be useful in morphine-induced psychological dependence in human as well

[ effect of chronic stress in pregnant mothers on the responsiveness to morphine in mice: a behavioral sensitization study]

The mechanisms which are plots for individual's willing to use Morphine are not yet recognized. Carried out researches indicated that tendency to narcotics is increased during stress or after it. In this research we studied the desire change of the second generation to morphine using induced restraint stress which is a kind of behavioral sensitization. This research was a kind of experimental interferer. At first mice were crossed after insuring about their pregnancy, Sub stress was put on them using special instruments. Some of the embryos head was cut to be studied histologically. After maturing their embryos in order to clarify their left and right handedness to be studied using T-Maze and they were compared with the control group. In order to find the effectiveness of the administrated acute morphine, five groups of stressed and non-stressed were chosen Both groups were divided into five: a control [without being injected], saline, Morphine 1 mg/kg, morphine 10 mg/kg and morphine 50 mg/kg. They were studied. Movement measuring done after being injected by open filled. Mentioned groups in the previous experiment, In order to determine their previous induced sensitization, were reexamined 48 hours after being injected 1 mg/kg morphine. Findings showed that the tissue thickness on the frontal cortex in stressed group was less than the control group [p<0.01] And also the number of stressed right handedness in males was less, but the number of left handedness in female ones was higher. Injection low dose morphine in experimental group had no effect, but in high dose caused induced motion activations. But this motion activity was much less than the control group. The low dose morphine injection [1 mg/Kg] in stressed groups caused induced motion activities which this action in dose 50 mg/kg was significant statistically [P<0/01]. Results showed that inducing a psychological relatively slight stress [a short-term restrain] could cause major changes, firstly in embryos brain and secondly in right handedness and left handedness and thirdly a response to morphine

Effects of the crocus sativus l. extract on the acquisition and expression of morphine-induced behavioral sensitization in female mice

The prevalence of opioid addiction is releativly high in Iran. Since the mechanism [s] of opioid addiction are not clear, this social problem is still remained unresolved. In the present study, the effects of water extract of Crocus sativus on the acquisition and expression of morphine-induced behavioral sensitization in female N-MARI mice [20-25 g] are investigated. Sensitization was induced by single injection of morphine [5 mg/kg] for three consecutive days followed by five days resting. On the 9th day of the experiments, the sensitization was assessed in animals by a single injection of very low dose of morphine [0.5 mg/kg]. The extract of the C. sativus was administered during or after induction of morphine sensitization. Then, the sensitization were tested in the animals. In order to evaluate the effects of the drugs on locomotor activity, morphine and the extract were administered to the animal in a pilot study. Our findings show that administration of morphine [0.5,5 and 50 mg/kg], induced a significant activity in animals. The increament was significant for the dose 50 mg/kg of morphine. On the other hand, administration of the plant extract [10, 50 and 100 mg/kg] also produced a significant hyperactivity and hypoactivity in the animals. Preadministration of the animals by extract [10, 50 and 100 mg/kg, i.p.] reduced morphine effects. Injection of the same extract [10, 50 and 100 mg/kg] 30 min before the morphine [5 mg/kg] administration in the traning days, caused a significant decrease in locomotor activity in animals, i.e. reduced the acquisition of morphine-induced behavioral sensitization. Injection of the plant extract [10, 50 and 100 mg/kg] in the test day, 30 min before morphine [0.5 mg/kg] administration also reduced the locomotor activity in the animals, i.e. reduced the expression of morphine-induced behavioral sensitization. It can be concluded that the extract of C sativus may inhibit morphine-induced hyperactivity and also acquisition and expression of morphine-induced behavioral sensitization in female mice which could be also usefull in human

[ effects of crocus sativus extract on the acquisition and expression of morphine-induced conditioned place preference in mice]

The effects of Crocus sativus [Saffron] on the euphoric properties of morphine have not yet been studied. In the present study, the effects of water extract of C. sativus stigma on the acquisition and expression of morphine-induced Conditioned Place Preference [CPP] in male N-MARI mice [weighted 20-25 g] were investigated. This experimental study was conducted on 136 male mice that were divided into 17 groups [n=8/group]. In a pilot study, different doses of morphine [1, 2, 4 and 8 mg/kg] and C. sativus extract [10, 50 and 100 mg/kg] were injected to the animals, to evaluate the drugs ability in induction of place preference. In the second phase of the experiments, the extract of the C. sativus was administered during or after induction of morphine CPP. Then, CPP were tested in the animals. One-way analysis of variance [ANOVA] was performed for statistical procedure. Administration of morphine [1, 2, 4 and 8 mg/kg], increased the required time in the compartment paired with morphine [i.e. CPP] that was significant [p<0.001] for those animals that received 4 and 8 mg/kg of morphine. Administration of the plant extract [50 mg/kg] also produced a significant CPP [p<0.01] compared with control group. Injection of the same dose of the extract before morphine [8 mg/kg] administration, caused a decrease in the time spent in drug-paired side only in dose of 100 mg/kg of the extract [p<0.05]. In addition, injection of the plant extract in the test days to the animals, which reveived morphine [8 mg/kg] in the conditioning days, enhanced the expression of morphine CPP in the animals, that was statisticaly significant for the extract at the concentration of 50 mg/kg [p<0.05]. It could be concluded that injection of the extract of C. sativus can inhibit the acquisition but enhanced the expression of morphine-induced CPP. In addition, the extract can produce CPP by itself

[Effects of nitric oxide on the expression of nicotine and apomorphine induced behavioral sensitization in mice]

Nicotine is the most abused drug in the world Experiments have shown that repeated administration of nicotine may increase the responsibility to the drug, whereas small amounts of nicotine may increase behavioral responses including locomotor activity. The aim of the present study was to investigate the role of nitric oxide and possible dopamine mediation in nicotine-induced behavioral sensitization. Since, it is hypothesized that dopaminergic pathways within the brain are responsible for sensitization, apomorphine has been used. Apomorphine was also used to evaluate the interactions between nitric oxide and brain dopaminergic pathways. In the present study, the effects of L-arginine [a nitirc oxide precursor] and L-NAME [a nitric oxide synthase inhibitor] on the acquisition and expression of nicotine-induced behavioral sensitization in female N-MARI mice [body weight 20-25 g n=7/group] were investigated. Animal activities were recorded by an infrared activity meter. In order to evaluate the effetcs of the drugs on animal locomotor activity, animals were received different doses of nicotine [0.25, 0.5, 0.75, 1 and 1.5 mg/kg], L-arginine [5, 10, 20 and 50 mg/kg], L-NAME [5, 10 and 20 mg/kg] apomorphine [0.125, 0.5 and 2 mg/kg]. L-arginine and/or L-NAME were injected to the animals either 20 min before each nicotine or apomorphine administration during the sensitization phase [acquisition] or 20 min before nicotine or apomorphine challenge dose [expression]. Results showed that administration of nicotine [1 mg/kg] caused significantly reduced, while apomorphine [0.125 mg/kg] significantly increased in animal's locomotor activity. While L-arginine administration did not change the animals' activities, injection of L-NAME [10 and 20 mg/kg] significantly reduced animals activities. Administration of L-arginine [5-50 mg/kg] before nicotine injection did not affect the nicotine-induced behavioral sensitization but did inhibit apomorphine-induced behavioral senitization. Injection of L-arginine [5-50 mgkg] reduced the expression of behavioral sensitization in nicotine and apomorphine senstized mice. L-NAME [5, 10 and 20 mg/kg] injection reduced both acquisition and expression of nicotine and apomorphine-induced behavioral sensitization. It could be concluded that inhibition of nitric oxide synthesis caused the inhibition of behavioral sensitization to nicotine and apomorphine. Considering these findings, it seems that nitric oxide inhibits nicotine-induced behavioral sensitization via brain dopaminergic pathways

[Effect of prenatal Morphine exposure on the Basal Ganglia development in rat embryo]

Investigations has showed that prenatal exposure to Morphine causes drug dependency and behavioral complications in new born rats. In this study effect of prenatal Morphine on the deveopment of basal ganglia in rat embryos is investigated. In this experimental study 36 female rats with body weight between 250-300 grams were selected. After crossing with male rats they were divided into six groups of 12 days control-Morphine, 14 days control-Morphin and 17 days control-Morphine groups. Morphine groups received 0.01mg/ml Morphine through their drinking water until the 12, 14 and 17[th] day of pregnancy [20 ml each rat]. Then rats were anesthetized and embryos were taken out and fixed. Their body weight and crown-rump length were measured. Then 5 micrometers sections were provided and stained using H and E method which were then evaluated using mutic program. Body weight and length of embryos were reduced significantly in the 12 and 14[th] day of Morphine group rats in compare to their controls. The significant reducation of Basal Ganglia thickness was also found in all Morphine groups compared to their controls. Results showed that prenatal Morphine exposure may cause impairment in change development of Basal Ganglia

[Effect of nucleus paragigantocellularis destruction on Caffeine and Naloxone withdrawal sings precipitations in male rats]

It is showed that the activity of paragiganocellularis [PGi] nucleus is diminished in addict animals, but in contrast this activity was augmented during withdrawal period. Also, regarding interrelation of opiate and adenosine systems, it was obvious that in each system not only the specific antagonists but also the contrast antagonists system could produce withdrawal signs. In this study the role of PGi nucleus in precipitation of withdrawal signs induced by opiate and adenosine antagonists was investigated. In this experimental study, dependency was induced by escalating doses of morphine via drinking water which were prescribed to the animals during a 21 days period. Then addicated rate were subjected to four groups: 1-Intact 2-Sham 3-unilateral PGi destruction and 4-bilateral PGi destruction. Withdrawal signs were induced by 1-Naloxone [2 mg/kg sc.] and 2-Caffeine [50 mg/Kg ip.] administration in each group. Data was gathered and then analyzed using one way ANOVA, Tukey and Chi square tests. P< 0.05 was considered significant. Naloxone withdrawal signs were consisted of diarrhea, ejaculation, teeth chattering, ptosis, irritability, wet dog shake, strop tail, jumping and weight loss. Following bilateral PGi destruction there was a marked attenuation in three signs of irritability, teeth chattering and jumping sings. The number of withdrawal signs which were produced by Caffeine administration were less than Naloxone [diarrhea, ejaculation, teeth chattering, chewing, irritability and jumping]. However, destruction of PGi nucleus [bilateral] diminished four sgins including: diarrhea, ejaculation teeth chattering, and irritability. The present study showed that the withdrawal signs precipitated with Caffeine are less different than Naloxone, and the bilateral PGi destruction could markedly attenuate these sings in Caffeine group more than Naloxone ones

[Effects of papaver rhoeas L. extract on the expression and development of morphine-induced conditioned place preference in mice]

In the present study, the effects of water-alcohol extract of Papaver rhoeas on the expression and acquisition of morphine-induced Conditioned Place Preference [CPP] in male N-MARI mice [20-25 g] were investigated. In a pilot study, different doses of morphine or the extract were administered to the animals to indicate whether the drugs could induce place preference in particular apparatus. In the second part of the experiment, the animals received different doses of extract 30 min before each morphine injection [acquisition] or 30 min before beginning of the test [expression]. Subcutaneous [SC] administration of morphine [1, 10 and 20 mg/kg] produced place preference. On the other hand, intra peritoneal [IP] administration of the plant extracts [25, 50 and 100 mg/kg] did not show any effect. Injection of extract [25, 50 and 100 mg/kg, IP] 30 min before the morphine administration decreased the acquisition of morphine CPP. Administration of the plant extract [25, 50 and 100 mg/kg, IP] 30 min before the test increased the expression of morphine-induced CPP. It could be concluded that the extract of Papaver rhoeas reduced the acquisition, but did not influence the expression of morphine-induced conditioned place preference in mice

[Effects of the Papaver rhoeas L. extract on naloxone-induced jumping behavior and diarrhea in morphine-dependent mice]

The prevalance of opioid addiction is releativly high in Iran. Since the mechanism [s] of opioid addiction are not clear, this social problem still remains unresolved. In the present study, the effects of water-alcohol extract of Papaver rhoeas on the acquisition and expression of morphine withdrawal in morphine-dependent N-MARI mice [20-25 g] were investigated. The animals became dependent to morphine and the extract of the Papaver Rhoeas was administered during and after induction of morphine dependence. Then, withdrawal syndroms were tested with naloxone [4 mg/kg] injection. Results showed that administration of naloxone after four days morphine treatment [12.5, 25 and 50 mg/kg], induced diarrhea and also increased the number of jumping in animals. The increase was significant for a dose of 50 mg/kg of morphine. On the other hand, administration of the plant extract [25, 50 and 100 mg/kg] did not induce any changes in the feaces or number of jumping behaviour in the animals. Injection of the same extract [25, 50 and 100 mg/kg] 30 min before morphine [50 mg/kg] administration, caused an increase in number of jumping but reduced the diarrhea in animals. Injection of the plant extract [25, 50 and 100 mg/kg] on the test day, 30 min before naloxone administration also decreased the number of jumping and diarrhea in morphine-dependent animals. It could be concluded that the extract of Papaver rhoeas can amilorates the withdrawal syndrom in morphine-dependent mice. Therefore, the extract might be useful for treatment of withdrawal signs in opioid addicts

[Effect of oral morphine administration on fertility of Balb/c mice]

In addition to have side effects on adults and embryos, abused drugs by affective sex and hypophysial hormones can reduce germ cells and sexual drive resulting infertility in human. Aim of this study is to evaluate the effects of addiction to morphine-induced infertility in Balb/c mice. For these purpose, a control [n=6] and 21 experimental [n=363] groups were used. Then oral morphine with initial doses [0.01, 0.05 and 0.1 mg/ml of water] in a 3 weeks period was administered to the animals and then the animals were crossed to each other. On 17th day of pregnancy, female rats were anesthetized by ether and the embryos were taken out surgically. Results showed that in all groups the birth chance were reduced according to the control group. The reduction was observed in group, which was treated with 0.01 morphine. Therefore it is concluded that morphine extremely reduced the birth chance in mice and may reduce fertility in animals and this may be reliable for human