جستجوی مقالات مرتبط با کلیدواژه "وابستگی به مرفین" در نشریات گروه "پزشکی"

Addiction as achronic disorder that requires long treatment. One way to treating this chronic disease is exercise. Chronic exposure to opiates impairs spatial learning and memory. Given the well-known beneficial effects of voluntary exercise on cognitive functions, we investigated whether voluntary exercise would ameliorate the cognitive deficits that are induced by morphine dependence. If an effect of exercise was observed, we aimed to investigate the possible role of hippocampal brain-derived neurotropic factor (BDNF)in the exercise-induced enhancement of learning and memory in morphine-dependent rats.

The rats were injected with bi-daily doses (10 mg/kg, at 12 hr. intervals) of morphine over a period of 10 days of voluntary exercise. Following these injections, a water maze task was performed twice a day for 5 consecutive days, followed by a probe trial 2 days later. A specific BDNF inhibitor (TrkB-IgG chimera) was used to block the hippocampal BDNF action during the 10 days of voluntary exercise.

The voluntary exercise diminished the severity of the rats’ dependency on morphine. A blockade of the BDNF action blunted the exercise-induced improvement of spatial memory, hippocampal neuron counting and BDNF protein levels in the dependent rats. Our results indicate that voluntary exercise could be increase the expression of LTP by lowering the induction threshold for LTP in the DG of morphine-dependent rats.

Thus, voluntary exercise might be considered as a potential method to ameliorate some of the deleterious behavioral consequences of the abuse of morphine and other opiates.

Exercise is one way to treat addiction. The aim of this study was to determine the improvement of spatial memory impairment following voluntary exercise in morphine-dependent rats.

In this experimental study, the sample rats received morphine (10 mg/kg) twice a day, 12 hours subcutaneously, at the same time as 10 days of running. All rats were then trained for 5 consecutive days and twice daily in the Mauritius water maze. Analysis of variance and Tukey’s test were used to analyze the data.

Comparison between groups showed that morphine-dependent and athletic control groups spent significantly more time in the target area than morphine-dependent and non-exercised control groups (respectively p=0.04 and p=0.0001) and this indicates that exercise improved spatial memory recall.

Voluntary exercise might be considered as a potential method to ameliorate some of the deleterious behavioral consequences of morphine abuse.

The long history of morphine consumption causes anxiety and behavioral disorders. Sport activities can have positive effects, especially via brain-derived neurotrophic factor (BDNF) on the brain. The purpose of this study was to investigate the effects of voluntary and compulsory exercise on anxiety-like behaviors and BDNF levels in hippocampus in morphine-dependent rats.
Rats were injected with bi-daily doses (10 mg/kg, at 12 hr intervals) of morphine for 10 days. Following, the rats in voluntary exercise were allowed to freely exercise in a running wheel for 10 days. The rats in the treadmill exercise groups were forced to run on a motorized treadmill for 30 min once a day for 10 days. Then, anxiety profile was tested using elevated plus maze (EPM) and light-dark box (L/D), and hippocampal BDNF was measured.
Morphine abstinent rats showed increased anxiety in both EPM and L/D box and reduced hippocampal BDNF. Enhanced anxiety, but not a decline in hippocampal BDNF was alleviated by both exercise regimens. Moreover, both exercises increased hippocampal BNDF and reduced anxiety in none-morphine treated rats.
This study showed that physical acivity could allivate the anxiety deficits in morphine abstienet rats probably through mechanisms that do not involve hippocampal BDNF. This suggests that physical acivity could be a potential therpeautic method to reduce anxiety disorders during abstience perioid.

Several Studies have identified that the mesocorticolimbic dopaminergic pathway consisting of the ventral tegmental area (VTA) and the nucleus accumbens (NAc) plays an important role in morphine dependence and withdrawal signs. Orexin projection and its receptors have been found in the brain regions including VTA that involved in the expression of morphine withdrawal signs. The aim of this study was to evaluate the effects of orexin receptor-1 (OX1R) agonist and antagonist microinjection into the VTA on withdrawal signs in morphine dependent rats. This experimental study was carried out on 24 male Wistar rats (weighing 250-300 g) in 2012 that were divided in 4 groups. They were rendered morphine dependent by subcutaneous injection of morphine sulfate at intervals of 12 h for 10 days. On day 11، intra-VTA microinjection of orexin receptor-1 agonist (orexin-A) and antagonist (SB-334867) was performed (2h after last morphine injection and before naloxan injection) and naloxone precipitated withdrawal sings were evaluated for 30 min. In the vehicle group، normal salin was microinjected into the VTA. Data were analyzed using t-test and ANOVA. Intra-VTA SB-334867 microinjection significantly decreased the jumping sign (P< 0. 01). Orexin-A microinjection significantly increased the wet-dog shakes sign (P< 0. 05). With regard to the results، OX1R in the VTA has a little effect on expression of withdrawal signs in morphine dependent rats.

Ocimum basilicum showed antinociceptive activity. The antinociceptive effect was inhibited by naloxone in hot-plate test. As O. basilicum antinociceptive activity was inhibited by an opioid antagonist, activity-guided fractionation of methanol extract of this plant was carried out to investigate the isolation of the active component(s) responsible for the alleviation of morphine withdrawal syndrome induced by naloxone. Dependence was induced using subcutaneous injections of morphine daily for three days (50, 50 and 75 mg/kg). On the fourth day, morphine was injected two hours prior to the intraperitoneal injection of naloxone. The number of jumps during the 30 minute period after naloxone injection was considered as measure of the withdrawal syndrome. The extract and fractions were injected 30 min prior to morphine injection. The methanol extract of plant was suspended in water and extracted with chloroform. The active chloroform layer was concentrated and partitioned between methanol-water (9:1) and petroleum ether. The extract or fraction was injected intraperitoneally at doses 0.15 - 1.46 g/kg. The methanol, chloroform and petroleum ether extracts decreased the jumping numbers more than the aqueous and hydro-alcohol extracts. Further fractionation on silica gel column chromatography yielded a fraction, which was 4 times as effective as the crude extract. The results of this study indicated that the plant extracts and fractions containing non- polar component (s) could be useful for the alleviation of morphine withdrawal syndrome

Adenosine has been considered as a fine-tuner of the neurotransmitters in the nerve system. Adaptive changes in the brain adenosine system occur in some patho-physiological situations such as chronic exposure to morphine. In this study, the adaptive changes in the adenosine deaminase activity as a key enzyme in the adenosine metabolism that converts adenosine to inosine and ammonia, irreversibly, due to morphine dependence and tolerance to anti-nociceptive effects of sodium-salicylate were investigated. Morphine dependence was induced by morphine administration in tap water (0.4mg/ml for 24 days). Tolerance to sodium-salicylate was induced by 6 i.p. injection (1 injection/day) of sodium-salicylate. Tolerance to antinociceptive effects of sodium-salicylate was measured by tail flick (TF) and hot plate (HP) tests. Right hippocampus was dissected, homogenized at phosphate buffer, centrifuged and then the supernatant fraction was isolated. Protein content of the samples was measured by the Bradford method. Hippocampus adenosine deaminase activity was measured by a calorimetric method of enzyme assay which is based on the direct measurement of the produced ammonia from excessive adenosine degradation by adenosine deaminase. Daily injection of Sodium-salicylate produced antinociception in early days by latency increase rather than saline injection (P<0.0001) but in the following days this antinociceptive effect progressively decreased so at the day 5 and 6 following injection it was similar to saline (P>0.05). Injection of morphine (5mg/Kg) at the day 7 showed more increase in the latency of saline injected rather than sadium-salicylate injected (P<0.001). Adenosine deaminase activity was significantly higher in sucrose administrated rather than chronic morhine administrated (P<0.05) and in saline injected rather than sodium-salicylate injected (P<0.05). Single injection of sodium-salicylate and its control shows the same activity. There was no significant difference in enzyme activity of morphine dependent with sadium-salicylate tolerance (P>0.05). This decline in the adenosine deaminase activity may be related with adaptation in brain adenosine system subsequent of dependent to morphine or tolerance to sodium-salicylate.

Bupropion is a unique, non-nicotinic smoking cessation agent despite its effective antidepression effect. It is a NE and DA reuptake inhibitor and as well as a nicotinic acetylcholine receptor antagonist. Beside its smoking cessation effects it can reduces some symptoms of nicotinic withdrawal signs. DA neurons such as VTA neurons play essential roles in depression and drug dependence. This study was tested the short-term effect of intra VTA injection of bupropion on naloxone precipitated withdrawal syndrome escape attendance and chewing signs. The sham group received saline as drug vehicle but treated groups received 0.25, 1.25 and 2.5 mg/μl/min of bupropion in VTA stereotaxically, and control group had surgery but had no any injection in VTA. Morphine dependence was carried out under standard protocol (i.p., 4 days, 3 time in each day with incremental doses 15, 20, 25, and 30 mg/kg). Withdrawal signs were precipitated by naloxone (1.2 mg/Kg, s.c.), observed continuously and registered on-line each minute. The behaviors captured by 3 digital cameras indifferent view (30 min) for offline analysis. Signs were counted and analyzed within and between groups by one-way ANOVA. The analysis of data showed that bupropion can decrease escape attendance behavior in a dose dependent approach but it can increase the chewing in dose dependent manure. The differences were significant between sham and treated groups. It concluded that bupropion can alter the opioid withdrawal signs in different directions and it can alter the pattern of withdrawal outcomes.

Background and In the present study, we compared the intensity of physical dependency, mortality rate and weight changes in some common methods for inducing morphine dependency. Six common different methods for morphine dependency were chosen in wistar rats. In all methods, morphine dependency was induced by repeated morphine injection. Precipitation of morphine withdrawal signs were performed on the last day in each method, 4 hours after the last morphine injection for 20 minutes. The withdrawal signs included: vertical jumping, wet dog shakes, diarrhea, teeth chattering, ptosis, head shakes and rearing. Our results demonstrated that all groups of treated rats showed withdrawal signs following naloxone challenge. However, the intensities of withdrawal signs (vertical jumping, wet dog shakes, diarrhea, teeth chattering, head shakes and rearing) were significantly different among these methods. Also, mortality rate and amount of weight loss were significantly different among the different methods. This study demonstrates that different experimental methods of morphine dependency can induce different intensities of withdrawal signs, mortality rate and weight loss.

N-methyl-D-aspartate (NMDA) receptors play a pivotal role in the development of tolerance and physical dependence to opiates. Activation of NMDA receptors involves the induction of long term potentiation (LTP) in hippocampus. Our previous study suggested that chronic oral administration of morphine enhanced NMDA dependent LTP in the CA1 area of hippocampal slices of rats. The present study examines the expression levels of individual NMDA receptor subunits, NR1, NR2A and NR2B, in the hippocampus of morphine-dependent rats by using western blotting. Total proteins of hippocampus were extracted by Tris-HCl buffer containing anti proteases and sodium dodecyl sulfate (SDS). The extracted proteins were resolved by SDS-PAGE and transferred to polyvinylidenefloride (PVDF) membrane by tank blotting and the subunits of NMDA receptor were analyzed by immunoblotting by using specific antibodies. Obtained results provide both biochemical and statistical evidence to suggest that NMDA receptor function in the hippocampus, at least in terms of expression of NR1, NR2A and NR2B protein subunits, increases in morphinedependent rats. Taken together, these data support several studies in the literature indicating that NMDA receptors in the hippocampus are involved in the process of opiate dependence.

The effects of acute and chronic exposures to opiate drugs on anxiety process are controversial. Acute morphine injection showed the beneficial effects on anxiety. Morphine withdrawal induced severe anxiety response in morphine dependence rats. Whereas, the effects of chronic administrations of morphine on anxiety process are less studied. Furthermore, this study was designed to assess the role of morphine dependence on the level of anxiety in Rat. In this experimental study, Twenty male Wistar rats (250-300 gr) were made dependent by chronic administration of morphine in drinking water that lasted at least 21 days. Control groups received only sucrose in their water. This study utilized the elevated plus- maze model to evaluate anxiogenic-like behavior in rats. Four fundamental behavior patterns were recorded for 5 minutes: the time spent on open arms, the number of entries into open arms, stretched-attend posture and defecation. Immediately after test, the locomotor activity of each animal was tested by using an automated activity monitor system. The data were analyzed by independent t-test and two-way analysis of variance (ANOVA). Finding indicated that the time spent on open arms and the numbers of entries into open arms were significantly shorter in morphine dependence group than control group (P<0.05). Also, the numbers of stretched-attend posture and defecation were significantly higher in morphine group (P<0.05). Whereas, there were no significant differences between groups in locomotor activity. This study showed that dependent rats may rapidly predispose anxiogenic- like effects in stressful conditions and without the effect on motor activity.

The nucleus accumbens is involved in various functions ranging from motivation and reward to feeding and drug addiction. Some researchers have also suggested that this region has some roles in consciousness. In the present study, the effect of electrical stimulation and lesion of nucleus accumbens on Electroencephalogram waves (EEG) of addict and non-addict rats was investigated. Male wistar rats (weight 190-250 g) were divided into control and addict groups. Addiction was induced by injection of morphine (three times a day and for four days). Then all rats in both groups were aneasthetized by urethane and stainless steel electrodes were implanted in nucleus accumbens. EEG waves were recorded in three stages of control, after stimulation (130µA, 100HZ, every 5sec for 10 min), and after lesion (0.4 mA, 60 sec) of nucleus accumbens in each group. In addict group alpha and betha waves were increased, while theta and dltha waves were decreased compared to intact group. Electrical stimulation and lesion of nucleus accumbens decreased theta waves in intact group and increased betha waves in addict group comparing to the control stages. Although morphine dependency causes increase of high frequency- low voltage waves and decrease of low frequency-high voltage waves, it seems, that nucleus accumbens has no role in variations of brain waves.

Opiates addiction is a phenomenon with complex physiological and social causes and consequences. The exact mechanisms of development of dependency and relapse remain unclear. Among the several possible mechanisms, the role of learning and memory in opiate dependency and relapse has received considerable attention in recent years. Therefore, in the current study the effect of morphine dependency induced by repeated subcutaneous injection of morphine on the above-mentioned parameters was examined. In this experimental study, animals in both dependent and withdrawal groups received morphine sulfate(10 mg/kg, s.c.) and normal saline was given to the control group. The administration of morphine sulfate and normal saline was done twice per day(8:00 AM & 8:00 PM) for 15 consecutive days. Dependent and control groups were observed from the 11th to 15th day but withdrawal animals were studied from the 16th to the 20th day. The animals were tested for four consecutive days(4 trials/day) to evaluate spatial learning process. During these 4 days(training days) the position of the hidden platform was unchanged. On the fifth day(probe trial) the platform was removed from maze to evaluate spatial memory process. The recorded spatial learning and memory parameters were subjected to ANOVA. The data showed that traveled times and distances to find the hidden platform, the mean of swimming speed on training days, and also the percentage of times and distances traveled in the target quarter in the probe trial stage were not statistically different among the studied groups. These findings clearly imply that morphine dependency induced by the current method has no significant effect on spatial learning and memory, which may result from a relative tolerance to morphine in dependent animals.

Opioids and morphine are increasingly abused in modern societies, especially in recent years. Therefore, the present study was designed to evaluate the effects of morphine depen-dency on rats’ sexual and maternal behaviors, birth rate, sex ratio and the rate of stillbirths. Adult male and female rats were allocated into treatment and control groups. The treatment group was sub-divided into two morphine-dependent groups, group I) consisting of a number of male couples and group II) of both parents. Morphine dependency was induced by gradual administration of oral morphine with a final dose of 0.4 mg/ml dispensed in drinking water for 14 days. Morphine dependency was confirmed by the observation of changes induced by naloxane administration. Sexual behavior was determined by vaginal plague obser-vation. Weight gain during pregnancy, rate of stillbirths, sex ratio, and maternity behavior (Caring for the neonates or eating them) were assessed in the groups. For statistical tests, one-way ANOVA with its non-parametric equivalent and for comparing means, 2 were used while employing SPSS software, version 13, for statistical analysis. The level of significance was regarded as p<0.05. A non-significant decline in sexual tendency was observed in groups I (60%) and II (67%), compared to the control group (80%). In the control group, 69% of all matings resulted in delivery compared to 39% and 38% in groups I and II respectively (p<0.05). Weight gain in groups I, II and the controls were 46±38, 28±28 and 62±33 grams respectively. Weight gain difference between the control group and group II was statistically significant (p<0.05). Sex ratio was 1.17, 1 and 1.57 in groups I, II and the controls, respectively. No stillbirths were seen in group I, while the rate of stillbirth in group II (67%) was statistically significant (p<0.001); one stillbirth was also seen in the control group. The rate of pup cannibalism in female rats on group II (37%) was significantly higher (p<0.001) than group I and the controls. Morphine dependency neither had effects on sex drive nor on fertilizing capacity in male or female rats but it increased the rate of pseudo-pregnancy. Morphine also increased the rate of stillbirths but it adversely affected maternal weight gain during pregnancy. Maternal beha-vior was highly affected by morphine dependency as well.