Morphine Withdrawal Symptoms In Rats Research Articles

Ascorbic Acid Effect on Morphine Withdrawal Symptoms in Rats

Introduction: Today, drug addiction is an important healthcare issue. Any helps to drug withdrawal may decrease its prevalence in the society. Ascorbic acid is a component, which can affect neurotransmitter systems as a regulator along with its cofactor role. Noradrenergic and dopaminergic systems are two important neurotransmitter systems in the opiate withdrawal syndrome. It seems that ascorbic acid can decrease the symptoms of opiate withdrawal through regulating the related systems. In this regard, the current study aimed to evaluate the effect of ascorbic acid on the symptoms of morphine withdrawal in Syrian mice.
 Materials and Methods: Male Syrian mice in eight experimental groups received incremental doses of morphine as 10, 20, 30 and 40 mg/kg within the first, second, third, and fourth days of the experiment, respectively, through intraperitoneal injection, twice a day, and the control group received and equal amount of saline. On the fifth day, six groups of morphine addicts received ascorbic acid with six doses of 10, 50, 100, 200,400 and 800 mg/kg through intraperitoneal injection. Then, naloxone 2 mg/kg was injected to all groups including morphine alone and morphine with acute does of ascorbic acid. Then, withdrawal symptoms were evaluated for 30 minutes.
 Results: Administration of an acute dose of ascorbic acid reduced dose dependent withdrawal symptoms in such a way that 10, 50, and 100 mg/kg doses of ascorbic acid reduced “writhing” symptom, 200 mg/kg reduced “jumping” symptom, and 400 and 800 mg/kg reduced “climbing, jumping, and standing” symptoms.
 Conclusion: It seems that ascorbic acid administration can improve the symptoms of opiate withdrawal syndrome. More studies on human population can also indicate the therapeutic effect of ascorbic acid on drug withdrawal.

Injection of D1 receptor antagonist SCH23390 into the periaqueductal gray attenuates morphine withdrawal symptoms in rats

The aim of this study was to investigate the relationship of dopamine D1 receptor (D1R) and its downstream factors with morphine withdrawal symptoms in rats. Rats were injected intraperitoneally with morphine in a dose-escalating manner. The midbrain periaqueductal gray (PAG) area was microinjected with D1R antagonist SCH23390 or D1R agonist SKF38393. Rats were intraperitoneally injected with naloxone (4 mg/kg) after the last morphine injection, and the withdrawal response was observed. The D1R antagonist reduced the withdrawal response in morphine-exposed rats and decreased the expression of Ca2+/calmodulin-dependent protein kinase II (CaMKII), phosphorylated extracellular signal-regulated kinase (p-ERK) and cAMP response element-binding protein (CREB) in the PAG. However, the ability of SKF38393 to increase the withdrawal response was weak and limited. Taken together, the results suggest that D1R antagonist decreased the withdrawal response in morphine-exposed rats by downregulating the downstream factors, CaMKII, p-ERK and CREB.

Effect of Hydro-alcoholic extract of Jasminum sambac on morphine withdrawal symptoms in rats

Effect of Hydro-alcoholic extract of Jasminum sambac on morphine withdrawal symptoms in rats

Effect of Hydro-alcoholic extract of Jasminum sambac on morphine withdrawal symptoms in rats

Effect of Hydro-alcoholic extract of Jasminum sambac on morphine withdrawal symptoms in rats

P.6.c.019 - Mefloquine attenuated morphine withdrawal symptoms in rat

P.6.c.019 - Mefloquine attenuated morphine withdrawal symptoms in rat

Effect of cupping on morphine withdrawal symptoms in rat

Effect of cupping on morphine withdrawal symptoms in rat

Orexin type 1 receptor antagonism in Lateral Paragigantocellularis nucleus attenuates naloxone precipitated morphine withdrawal symptoms in rats

Orexin neuropeptides have been reported to be involved in morphine induced physical dependence and withdrawal. The Lateral Paragigantocellularis (LPGi) is a key brain region implicated in the expression of somatic signs of morphine withdrawal syndrome. Orexin A and orexin type 1 receptor have been found in LPGi neurons but the effect of orexin on the expression of opiate dependence and withdrawal phenomena in this brain structure has not been studied yet. In this study, the effect of intra-LPGi administration of SB 334867 (selective orexin type 1 receptor antagonist) on the behavioral signs of morphine withdrawal syndrome was investigated. Male Wistar rats weighing 250–300g were rendered dependent by adding morphine sulfate (Temad, Tehran, Iran) to their drinking water in increasing concentrations of 0.1, 0.2, 0.3mg/ml for every 48h and 0.4mg/ml during the next 15 days. Behavioral signs of morphine withdrawal were assessed in a transparent cylindrical Plexiglas test chamber (30cm diameter, 50cm height) for 25min. One group of animals received intra-LPGi injection of SB 334867 (0.2μl, 100μM) immediately before naloxone. In the control group, SB-334867 vehicle (DMSO 1%, 0.2μl) was microinjected into LPGi. Our results indicate that intra-LPGi administration of SB 334867 significantly decreases naloxone precipitated morphine withdrawal signs. Thus, it seems that orexin might have a pivotal role in the expression of morphine withdrawal signs through affecting orexin type 1 receptor in LPGi nucleus.

P03-527 - The effects of Ascorbic acid on morphine withdrawal symptoms in rats

BackgroundRecent studies indicate that the glutamatergic and Dopaminergic systems are also involved in morphine tolerance and dependence on morphine and in morphine withdrawal syndrome. Ascorbic acid (ascorbate) which is an antioxidant vitamin released from glutamatergic neurons and modulate the synaptic action of dopamine and glutamate as well as behavior. Since Ascorbate modulate the synaptic action of dopamine and glutamate, in this study the effect of Ascorbate on morphine withdrawal syndrome in rats has been investigated.Objectiveto determine the effects of Ascorbic acid on morphine withdrawal syndrome.Methods30 Male rats (250–300 gr) were tested in this study in two group, The first group as the control group received 3% sucrose in tap water(n = 6) and the second group as the dependent group received morphine (0.1, 0.2, 0.3, 0.4 mg/ml each one for 48 h, and 0.4 mg/ml remaining days to 21st days) and 3% sucrose in tap water (n = 24) , this group divided in to 4 sub groups: ((1) morphine group, [2,3,4] morphine-Ascorbic acid groups which received AA (100,500,1000 mg/kg I.P) every 48h and in the end (21st day) 30 min before naloxone administration for evaluation effects of AA on withdrawal signs.FindingOur results show that: Ascorbate (100, 500, 1000 mg/kg I.P) can greatly attenuates most of morphine withdrawal syndrome(but not all) dose dependently.

P03-40 The effects of Locus coeruleus inactivation on I.V self administration of morphine and morphine withdrawal symptoms in rats

Biochemical, behavioral, and electrophysiologic studies indicate that activation of the noradrenergic cells in the Locus coeruleus (LC) play an important role in the symptoms of opiate withdrawal. There for in this study the effects of LC inactivation on self-administration of Morphine and on morphine withdrawal syndrome in rats has been investigated.Male rats (250-300gr) were anaesthetized and implanted with silastic catheters inserted in to the right jugular vein. after 5 days animals were fitted and the external end of the catheter was connected with a syringe-driven pump, then were placed in the self-administration apparatus that had two lever (active, passive) for 2 h every day. Active lever switched on the infusion pump for 10 sec, injecting. 1ml of saline or saline containing 5 mg/ml of morphine (training period was 10days). LC was inactivated by (1ul) lidocaein (%2) five min befor training.Animals were allowed to self administer morphine (1mg/kg per inf.) ten consecutive daily 2-h session. During all morphine self administration session lever pressing behavior was measured. Our results show that LC inactivation 5min before morphine self administration produced a significant decrease in the initiation of morphine self administration during all session. after the last test session morphine withdrawal symptom signs (MWS) precipitated by naloxone were measured. Our results show that most of MWS (but not all) were decreased by LC inactivation in comparison with morphine group.

Chronic infusion of clonidine does not alleviate spontaneous morphine withdrawal symptoms in rats

Opiate withdrawal is associated with behavioural symptoms and a sympathetic hyperactivity, the latter being sensitive to clonidine. The central question is whether behavioural symptoms would be also sensitive to clonidine. A rat model was used in which the locomotor activity was measured 24 h a day during the morphine withdrawal phase. Spontaneous withdrawal of morphine reduced strongly the high nocturnal locomotor activity, concomitantly decreasing food intake and body weight. Chronic infusion of clonidine (30-120 micrograms/kg/day) using osmotic minipumps had no effect on the withdrawal symptoms. Higher dosages (250-1000 micrograms/kg/day) potentiated rather than alleviated the withdrawal symptoms, suggesting an alpha 1-adrenergic effect of clonidine rather than an alpha 2-action. Therefore, we studied the action of a more specific alpha 2-agonist UK-14.304. UK-14.304 was less potent than clonidine in naive animals. It slightly alleviates the decrease of nocturnal activity during spontaneous morphine withdrawal. Furthermore, we have tested whether the effects of high dosages of clonidine could be altered by a specific alpha 1-antagonist doxazosine. Doxazosine reduced only slightly the potentiation in the decrease in food intake by clonidine during morphine withdrawal. For the other symptoms no interaction between doxazosine and clonidine was found. The data suggest that the use of clonidine in the detoxification of opiate dependent people is based on the suppression of the sympathetic hyperactivity rather than on symptoms with a more behavioural character.

Effects of alpha 2-agonists on morphine withdrawal behaviour: potentiation of jumping mediated by alpha 2-receptors.

Clonidine has a dual action on naloxone-precipitated morphine withdrawal symptoms in rats: a suppressive action on body shakes and body weight loss and a potentiating action on jumping and aggression. It has been suggested that this potentiating, excitatory action is mediated by alpha 1-receptors. More specific alpha 2-agonists therefore should have a less excitatory effect on the latter symptoms. This hypothesis has been studied in rats dependent on morphine. Withdrawal was precipitated using naloxone. Prior to naloxone the alpha 2-agonists clonidine, guanfacine, azepexole, BHT-920, UK 14304 or the centrally acting alpha 1-agonist ST 587 were administered. All alpha 2-agonists but not the alpha 1-agonist potentiated the jumping and decreased body shakes and body weight loss. The effects of clonidine and azepexole were characterized pharmacologically using the alpha-antagonists yohimbine and prazosin. Jumping potentiated by clonidine was antagonized by yohimbine whereas prazosin had no effect. Azepexole induced jumping was decreased by yohimbine both with respect to incidence and frequency, whereas prazosin only lowered the frequency. The suppressive actions of clonidine and azepexole on body shakes were reversed by yohimbine and not by prazosin. The data indicate that the potentiation of jumping by alpha 2-agonists as well as the suppression of body shakes in morphine withdrawal behaviour is mediated by alpha 2-receptors.

The effects of bilateral cingulate cortex lesions on morphine withdrawal symptoms in rats

In order to test the hypothesis that bilateral cingulate cortex lesions prevent opiate dependence and associated withdrawal symptoms, rats were given access to sucrose morphine solutions and subsequently challenged with nalorphine, an opiate antagonist. Animals with cingulate cortex lesions lost more weight following the nalorphine challenge than other animals, indicating that the lesions do not prevent withdrawal symptoms. On the contrary, the lesions are associated with more severe symptoms, and by inference, physiological dependence as well.