Attenuation of Morphine-Induced Tolerance and Dependence by Pretreatment with Cerebrolysin in Male rats

Drug Research ◽  
2017 ◽  
Vol 68 (01) ◽  
pp. 33-37 ◽  
Author(s):  
Hamed Ghavimi ◽  
Sara Darvishi ◽  
Saeed Ghanbarzadeh
Keyword(s):  
Male Rats ◽  
Control Group ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Attenuation Effect ◽  
Morphine Administration ◽  
Male Wistar Rats ◽  
Potent Growth ◽  
Induced Tolerance ◽  
Withdrawal Signs

Abstract Background Dependence and tolerance to morphine are major problems which limit its chronic clinical application. Purpose This study was aimed to investigate the attenuation effect of Cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,), on the development of Morphine-induced dependence and tolerance. Methods Male Wistar rats were selected randomly and divided into different groups (n=8) including: a control group, groups received additive doses of morphine (5–25 mg/kg, ip, at an interval of 12 h until tolerance completion), and groups pretreated with Cerebrolysin (40, 80 and 160 mg/kg, ip, before morphine administration). Development of tolerance was assessed by tail-flick test and the attenuation effect of Cerebrolysin on morphine-induced dependence was evaluated after injection of naloxone (4 mg/kg, ip, 12 h after the morning dose of morphine). Seven distinct withdrawal signs including: jumping, rearing, genital grooming, abdominal writhing, wet dog shake and teeth grinding were recorded for 45 min and total withdrawal score (TWS) was calculated. Results Results showed that administration of Cerebrolysin could prolonged development (10 and 14 days in administration of 80 mg/kg and 160 mg/kg Cerebrolysin) and completion (4, 10 and 14 days in administration of 40, 80 and 160 mg/kg Cerebrolysin, respectively) of tolerance. Results also indicated that administration of Cerebrolysin (40, 80 and 160 mg/kg) could significantly decreased the TWS value (62±2, 77±4 and 85±6%, respectively). Conclusion In conclusion, it was found that pretreatment with Cerebrolysin could attenuated morphine-induced tolerance and dependence.

scholarly journals Possible Involvement of Serotonergic Mechanism(s) in the Antinociceptive Effects of kaempferol

2020 ◽  
pp. 64-70
Keyword(s):  
Locomotor Activity ◽  
Receptor Antagonist ◽  
Serotonin Receptors ◽  
Metabolic Diseases ◽  
Male Rats ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Way 100635 ◽  
Antinociceptive Effects ◽  
Male Wistar Rats

Background and Objectives: A flavonoid kaempferol (KM) exerts an anti-inflammatory effect and is reportedly capable of preventing metabolic diseases. Nonetheless, a limited number of studies have been carried out on the antinociceptive effects of kaempferol. Objectives: The present study aimed to investigate the involvement of serotonin receptors in the antinociceptive-like activity of KM in male Wistar rats using the tail-flick test. Materials and Methods: The compounds (i.e., KM, morphine, and diclofenac) were intracerebroventricularly administered to rats for the examination of central effects on the thermal pain using the tail-flick test. For the evaluation of the involvement of serotonin receptors in the possible antinociceptive effects of kaempferol, several antagonists (i.e., tropisetron, ketanserin, GR113808, WAY 100635, and penbutolol) were used. Additionally, locomotor activity and motor responses were investigated by the rotarod test after KM treatment. Results: The intracerebroventricular microinjections of KM showed antinociceptive effects using the tail-flick test. The pretreatment with tropisetron as a 5-HT3 receptor antagonist at 1 and 10 mg completely reversed the KM-related antinociception. Furthermore, ketanserin (5-HT2A receptor antagonist) and GR113808 (5-HT4 receptor antagonist) both at 10 mg reduced KM-related antinociception; however, 5-HT1A receptor antagonist WAY 100635 and 5-HT1B antagonist penbutolol did not decrease KM-related antinociception. All KM doses were not observed with a significant effect on locomotor activity or motor reactions. Conclusion: The results of the current study suggested that serotonergic receptors (i.e., 5-HT2A, 5-HT3, and 5-HT4) are effective in the KM antinociceptive activity in male rats.

scholarly journals Effect of Hydroalcoholic Extract of Hyssop on Acute Pain in Male Rats Using Tail Flick Test

2021 ◽  
Vol 2 (1) ◽  
pp. 15-19
Author(s):  
Amir Larki-Harchegani ◽  
Abbas Ehsanikia ◽  
Sara Ataei ◽  
Fakhriosadat Hosseini ◽  
Rasool Haddadi
Keyword(s):  
Analgesic Effect ◽  
Positive Control ◽  
Male Rats ◽  
Saline Control ◽  
Control Group ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Hydroalcoholic Extract ◽  
Analgesic Effects ◽  
Iranian Traditional Medicine

Background: Iranian traditional medicine uses hyssop (Hyssopus officinalis) as an effective medicinal plant to reduce pain and inflammation in different diseases. Although the anti-inflammatory effect of this plant is proved, there is no study into its analgesic effects. Thus, this study aimed to investigate the analgesic effect of the hydroalcoholic extract from hyssop flowers and upper branches. Methods: This experimental study was conducted on 66 male rats that were divided into several groups including a saline control group, the groups of different doses of hyssop extract, morphine positive control group, the groups of hyssop extract plus morphine, and the most effective dose of the hyssop extract plus naloxone. All injections were administered intraperitoneally, and the pain was measured through the tail flick test. Results: Based on the results, 600 mg/kg was the most effective analgesic hyssop extract dose, and the most analgesic effect was observed at 45 minutes after administration. In addition, the administration of the most effective extract dose (600 mg/kg) plus morphine significantly improved the analgesic effects of morphine (P<0.001). Finally, the administration of naloxone plus the most effective extract dose (600 mg/kg) significantly reduced the analgesic effect of the extract (P<0.05). Conclusion: Overall, the hydroalcoholic extract of hyssop has analgesic effects that are probably applied through opioid receptors.

Optimal interval for hot water immersion tail-flick test in rats

2013 ◽  
Vol 26 (4) ◽  
pp. 218-222 ◽  
Author(s):  
Quanhong Zhou ◽  
Yuhua Bao ◽  
Xin Zhang ◽  
Lulu Zeng ◽  
Li Wang ◽  
...  
Keyword(s):  
Water Immersion ◽  
Hot Water ◽  
Male Rats ◽  
Laboratory Animals ◽  
Control Group ◽  
Tail Flick ◽  
Sprague Dawley ◽  
Tail Flick Test ◽  
Optimal Interval ◽  
Hot Water Immersion

BackgroundThe hot water tail-flick test is widely used to measure the degree of nociception experienced by laboratory animals. This study was carried out to optimise interval times for the hot water immersion tail-flick tests in rats.MethodTen different intervals from 10 s to 1 h were tested in 60 Sprague–Dawley male rats. At least eight rats were tested for each interval in three consecutive hot water tail-flick tests. Dixon's up-and-down method was also used to find the optimal intervals. The same rats were then divided into two groups. In Group N, naloxone was injected to reverse the prolonged latency times, whereas saline was used in the control Group S.ResultsIntervals of 10 s, 20 s, 30 min and 1 h did not significantly impact latencies, yielding similar results in three consecutive tests (p> 0.05). However, interval times of between 30 s and 20 min, inclusively, caused significantly prolonged latencies in the second and third tests (p< 0.001). Dixon's up-and-down method showed that 95% of the rats had prolonged latencies in hot water tail-flick tests at intervals longer than 32 s. Naloxone reversed prolonged latencies in Group N, whereas the latencies in Group S were further prolonged in 5 min interval tests.ConclusionThe optimal intervals for hot water tail-flick tests are either shorter than 20 s or longer than 20 min. The prolonged latencies after repetitive tests were attributable to an endocrine opioid.

Paroxetine effects on morphine analgesic tolerance in rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Navideh Sahebi Vaighan ◽  
Soha Parhiz ◽  
Masoumeh Sabetkasaei ◽  
Taraneh Moini Zanjani ◽  
Malek Zarei
Keyword(s):  
Intraperitoneal Injection ◽  
Tolerance Induction ◽  
Morphine Tolerance ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Analgesic Tolerance ◽  
Progressive Decline ◽  
Morphine Administration ◽  
Male Wistar Rats ◽  
Daily Intraperitoneal Injection

Abstract Objectives To alleviate different pain intensities, morphine administration has been extensively used. However, prolonged administration of morphine leads to a progressive decline of its analgesic effect which limits their overall utility. Morphine tolerance is considered as a challenging issue for the treatment of both acute and chronic pain. We conducted this study in rats to investigate the effect of paroxetine on morphine tolerance when used preemptively or after morphine tolerance had developed. Methods Male Wistar rats (weight 250–300 g, n=10) were used to evaluate the effects of paroxetine on tolerance to morphine. In order to induce tolerance, daily intraperitoneal injection of morphine (7 mg/kg) was done. After tolerance induction, a group of animals received intraperitoneal injection of 10 mg/kg paroxetine 30 min prior to each morphine dose. In another trial, to investigate the potential of paroxetine to prevent tolerance to morphine, animals were pretreated with 10 mg/kg paroxetine 30 min before morphine administration. In the control groups, 10 mL/kg of saline was injected. The behavioral test (tail-flick test) was done for all groups. Results Our data showed that paroxetine significantly reversed tolerance to morphine when used after tolerance induction (p<0.001). However, administration of paroxetine before occurrence of tolerance had no effect. Conclusions We conclude that paroxetine could decrease tolerance to morphine when used after the occurrence of morphine tolerance, while it was not able to prevent morphine tolerance when administered preemptively. Ethical committee number IRIB.SBMU.MSP.REC.1394.098.

Chronic immobilization stress induces anxiety-related behaviors and affects brain essential minerals in male rats

2020 ◽  
pp. 1-8
Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  
Keyword(s):  
Immobilization Stress ◽  
Central Area ◽  
Essential Elements ◽  
Male Rats ◽  
Control Group ◽  
Male Wistar Rats ◽  
Swimming Test ◽  
The Brain ◽  
Center Area ◽  
Chronic Immobilization Stress

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.

scholarly journals Effects of Electroacupuncture on Pain Threshold of Laboring Rats and the Expression of Norepinephrine Transporter andα2 Adrenergic Receptor in the Central Nervous System

2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Qianli Tang ◽  
Qiuyan Jiang ◽  
Suren R. Sooranna ◽  
Shike Lin ◽  
Yuanyuan Feng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adrenergic Receptor ◽  
Pain Threshold ◽  
Norepinephrine Transporter ◽  
Control Group ◽  
Tail Flick ◽  
Pregnant Rats ◽  
Tail Flick Test ◽  
The Central Nervous System

To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter andα2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, andα2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET andα2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels ofα2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects.

Acute and subchronic co-administrations to cadmium, diazinon and selenium induce apparent osteoporotic symptoms in adult male rats

Biologia ◽  
2014 ◽  
Vol 69 (10) ◽  
Author(s):  
Hana Ďúranová ◽  
Monika Martiniaková ◽  
Ivana Boboňová ◽  
Radoslav Omelka ◽  
Robert Stawarz ◽  
...  
Keyword(s):  
Adult Male ◽  
Osteoporotic Fractures ◽  
Bone Diseases ◽  
Male Rats ◽  
Control Group ◽  
Femoral Bone ◽  
Negative Effects ◽  
Young Males ◽  
Male Wistar Rats ◽  
Group B

AbstractCadmium (Cd) and diazinon (DZN) are known to be environmental risk factors for various bone diseases including osteoporosis. Selenium (Se), an essential constituent of many antioxidant enzymes, has in higher concentrations negative effects on the bone. The present study was aimed to investigate possible changes in femoral bone of adult male rats after their acute and subchronic exposures to Cd, DZN and Se. A total of 30 male Wistar rats were randomized into three experimental groups. The rats in the group A (4-months-old) were injected intraperitoneally with a mixture of 2 mg CdCl2 kg−1, 20 mg DZN kg−1 and 2 mg Na2SeO3 kg−1 body weight and killed 36 h after xenobiotics had been injected. In the group B, young males (1-month-old) were administered with a combination of 30 mg CdCl2 L−1, 40 mg DZN L−1 and 5 mg Na2SeO3 L−1 in their drinking water, for 90 days. Ten 4-months-old males without toxicant supplementation served as a control group (C). After treatment period, detailed histological analysis of femoral bone was performed in each group. Our results revealed apparent osteoporotic symptoms (resorption lacunae, osteoporotic fractures) in rats from groups A and B. Moreover, histomorphometrical evaluation showed reduced bone vascularization (constricted primary osteons’ vascular canals and Haversian canals) and weakness mechanical properties of bones (smaller size of the secondary osteons) in these rats in comparison with those of the control group. Our study demonstrates for the first time that acute and subchronic co-administrations to Cd, DZN and Se induce evident manifestation characteristics of osteoporosis in male rats.

scholarly journals Upregulation of Kiss-1 and Gpr54 Genes Expression in Pituitary of Male Rats Following the Central Administration of Neuropeptide Y

2019 ◽  
Vol 4 (4) ◽  
pp. 137-142
Author(s):  
Vahid Azizi ◽  
Shahrbanoo Oryan ◽  
Homayuon Khazali ◽  
Abdolkarim Hosseini
Keyword(s):  
Gene Expression ◽  
Pituitary Gland ◽  
Neuropeptide Y ◽  
Wistar Rats ◽  
Third Ventricle ◽  
Male Rats ◽  
Control Group ◽  
Central Administration ◽  
Reproductive Axis ◽  
Male Wistar Rats

Introduction: The neuropeptide Y (NPY) in the neural circuits of the hypothalamus has a stimulating effect on reproductive activities in mammals. Kisspeptin (KiSS1) is a quintessential neurotransmitter in the reproductive axis which directly stimulates gonadotropin-releasing hormone neurons in the hypothalamus. The distribution of KiSS1 expressing cells in the pituitary was described previously. Despite earlier reports showing the KiSS1 receptor, G-protein coupled receptor 54 (GPR54) expression in the pituitary, the potential physiological roles of kisspeptin at this gland have remained obscure. Accordingly, this study investigated the role of NPY on the relative expression of Kiss1 and Gpr54 genes in the pituitary gland in male Wistar rats. Methods: In general, 20 male Wistar rats weighing 200-250 g in 4 groups (5 in each group) received saline, NPY (2.3 nM), BIBP3226 (NPY receptor antagonist, 7.8 nM), and NPY+ BIBP3226. Then, they received the simultaneous injection of these molecules through the third ventricle of the brain. Finally, the relative mean expressions of Kiss1 and Gpr54 genes in the anterior pituitary were quantitatively analyzed by the real-time polymerase chain reaction. Results: The central injection of NPY increased the relative mean expressions of Kiss1 and Gpr54 genes in the pituitary gland compared to the control group although the injection of BIBP3226 eradicated these effects. However, the gene expression of Gpr54 in the rats receiving NPY coupled with BIBP3226 in hypophysis in comparison to the group receiving only NPY demonstrated a significant reduction (P<0.05). Conclusion: Overall, the central injection of NPY stimulated the gene expression of Kiss1 and Gpr54 in the pituitary gland.

scholarly journals The Effect of Herniarin on Spatial Working Memory, Pain Threshold, and Oxidative Stress in Ischemic Hypoperfusion Model in Rats

2021 ◽  
Vol 7 (1) ◽  
pp. 42-50
Author(s):  
Zahra Nazari Barchestani ◽  
◽  
Maryam Rafieirad ◽  
Keyword(s):  
Oxidative Stress ◽  
Pain Threshold ◽  
Male Rats ◽  
Control Group ◽  
Tail Flick ◽  
Pain Thresholds ◽  
Ischemic Group ◽  
Significant Difference ◽  
The Brain ◽  
And Oxidative Stress

Background: Ischemia causes severe neuronal damage and induces oxidative stress, memory impairment, and reduces pain threshold. Herniarin is a powerful antioxidant. Objectives: This study aimed to evaluate the effect of herniarin on memory, pain, and oxidative stress in an ischemia model in male rats. Materials & Methods: In this study, 50 male rats were divided into 5 groups of control, sham, ischemic, and two other ischemic groups, which received herniarin at doses of 150 and 300 mg/kg by gavage for 14 days. Behavioral tests were performed by shuttle box, and Y-maze and pain tests were performed by Tail-Flick test. Then, the rats’ brains were extracted to evaluate lipid peroxidation and measure the levels of thiol and Glutathione Peroxidase (GPX) in the hippocampus and striatum tissues. The results were expressed as Mean±SEM and then analyzed using suitable statistical methods of ANOVA and least significant difference post-hoc test in SPSS V. 20. Results: Herniarin significantly increased the avoidance memory, spatial memory, and pain thresholds of ischemic rats at different concentrations (P<0.001). Besides, the amount of malondialdehyde (MDA) and thiol in the ischemic group increased significantly in comparison to the control group (P<0.001). Also, in the ischemic group, GPX (P<0.001) significantly decreased. Decreased MDA (P<0.001) and thiol (P<0.001) and increased GPX levels were observed with herniarin administration (P<0.01). Conclusion: According to this study’s results, herniarin can remove free radicals and oxidant substances from the brain. Thus, it improves memory and pain thresholds in the brain hypoperfusion ischemia model.

scholarly journals Comparing the Antinociceptive Effects of Methamphetamine, Buprenorphine, or Both After Chronic Treatment and Withdrawal in Male Rats

2019 ◽  
Vol 10 (4) ◽  
pp. 313-322
Author(s):  
Farshid Etaee ◽  
◽  
Arezoo Rezvani-Kamran ◽  
Mohammad Taheri ◽  
Ghazaleh Omidi ◽  
...  
Keyword(s):  
Pain Perception ◽  
Synergistic Effects ◽  
Reaction Times ◽  
Male Rats ◽  
Tail Flick ◽  
Hot Plate ◽  
Analgesic Effects ◽  
Antinociceptive Effects ◽  
Male Wistar Rats ◽  
Post Hoc

Introduction: Methamphetamine (Meth) and Buprenorphine (BUP) modulate pain perception. However, the antinociceptive effects of their interactions, which affect through different systems, are unclear in rats. This study aimed to compare the analgesic effects of Meth, BUP, and their coadministration, as well as the effect of withdrawal from these substances on nociception in male rats. Methods: In this experiment, 40 male Wistar rats (weight: 250-300 g) were categorized into four groups: control, Meth, BUP, or BUP+Meth. After seven days of treatments, the antinociceptive effects were assessed using the hot plate and the tail flick tests. The differences among the groups were analyzed with ANOVA and Tukey’s post hoc tests. P values less than 0.05 were considered significant. Results: Meth and BUP increased the reaction times during the hot plate and tail flick tests. The combination of Meth and BUP increased reaction time more than Meth or BUP alone.  Conclusion: The significantly high reaction times in rats treated with Meth and BUP indicate that these substances have antinociceptive effects. In addition, Meth enhanced the antinociceptive effects of BUP. These synergistic effects might occur through the dopaminergic, serotonergic, and or adrenergic systems.

Sign in / Sign up

Export Citation Format

Share Document