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Showing 9 results for Morphine Withdrawal

Valiolah Hajhashemi, Taghi Ghafghazi, Mohammad Reza Nikravan,
Volume 6, Issue 1 (4-2002)

Recent studies have shown that NMDA receptors are involved in the tolerance and dependence to opioids. In addition, it has been reported that ketamine, dextromethorphan and amantadine have antagonistic activity at NMDA receptors. Therefore, this study was conducted to clarify the effect of these drugs on morphine withdrawal syndrome. Morphine dependence was induced by increasing doses of morphine (30, 45, 60, and 90 mg/kg, s.c.) administered at 2 h intervals. Dextromethorphan (12.5, 25, and 50 mg/kg), amantadine (50, 100, and 150 mg/kg), ketamine (50 mg/kg), and clonidine (0.2 mg/kg) were injected (i.p.) 90 minutes after the last injection of morphine. Furthermore, these drugs were administered orally 60 minutes after the last morphine injection. All animals received naloxone (5 mg/kg, i.p.) 2 h after the last morphine injection. Withdrawal syndrome (number of jumping, standing on feet. and diarrhea) was recorded during a 30-min period. Dextromethorphan and amantadine inhibited jumping, standing on feet and diarrhea in a dose-dependent manner. Ketamine (50 mg/kg) had a similar effect and clonidine produced an almost complete inhibition of withdrawal syndrome. Although these test drugs belong to different pharmacological classes, but they share NMDA receptor antagonistic effect and it may be the probable cause for inhibition of withdrawal syndrome.

Volume 9, Issue 2 (11-2005)

Narges Kerachian, Hojjatollah Alaee, Mahin Gharavi-Naini, Aliasghar Pilevarian, Ali Moghimi,
Volume 10, Issue 4 (1-2007)

Introduction: Previous studies have suggested that plants Avena sativa, Hypericum perforatum, Passiflora incarnata and Lavandula officinalis can affect nervous system and reduce neural excitability and pain. The aim of this study was to evaluate the effect of a mixture of these four plant’s alcoholic extract on morphine withdrawal symptoms. Methods: Experiments were performed on four animal groups of Wistar rats weighing 250-300 g (N= 7). For addiction induction, increasing doses of morphine were injected (Intraperitonealy (i.p.)) during nine days. After scientific identification, the plants were dried in room temperature and pulverized. Four plants powder were mixed with same proportion and then extracted using ethylic alcohol 70% by percolation method and then concentrated by rotary, and administrated at the dose of 400 mg/kg in all experimental groups. Morphine withdrawal syndrome symptoms include standing, stretching, jumping, Limbs shaking, blinking, ptosis, were recorded for 30 minutes. Results: Analysis of results showed a significant reduction of withdrawal symptoms in experimental groups (post and co -treated) in comparison with sham group.. Administration of extract cocktail prior to naloxone induced precipitation of withdrawal syndromes, reduced the expression of syndrome signs. Conclusion: It seems that administration of extract cocktail of these four plants inhibits both development and expression of morphine physical dependence symptoms. Considering the effects of different substances of above mentioned plants on excitability and anxiety mechanisms of the brain, the results of this study support the traditional application of these plants.
Khadije Gholami, Mahnaz Kesmati, Reza Kazeminejhad, Faride Zangene, Abdoalrahman Rasekh,
Volume 11, Issue 1 (4-2007)

Introduction: Some studies indicate changes in the level of thyroid hormones in addicted people. Also, there are some reports concerning the modulation of hypothalamus-hypophysis-thyroid axis in the context of morphine addiction. In the present study, the effects of thyroid gland activation via the acute and chronic administration of levothyroxine on morphine withdrawal syndrome were investigated. Methods: Frothy two adult male mice were divided into 6 groups. Animals received three daily injections of morphine (20, 40, 80 mg/kg) alone or in combination with l-thyroxin (0.5 mg/kg, i.p: single dose, chronic for 4 days and chronic for 16 days). Morphine withdrawal syndrome was induced using naloxone. Withdrawal signs such as jumping, rearing, climbing and weight loss were recorded for 30 minutes. Results: The results showed that acute levothyroxine administration increased the morphine withdrawal signs. Four days administration of levothyroxine reduced the number of jumping and climbing and inhibited weight loss. Administration of levothyroxine for 16 days reduced only the number of rearing. Conclusions: It seems that levothyroxine via alteration of thyroid hormones level can affect morphine withdrawal signs and this effect of levothyroxine can be attenuated with its repetitive administration.
Hossein Azizi, Saeed Semnanian, Seyed Javad Mirnajafizadeh,
Volume 15, Issue 2 (8-2011)

Introduction: It has been shown that orexin peptides have a role in opioid withdrawal behaviors. Orexin-expressing neurons that are present in the hypothalamic nuclei send dense projections to the Locus Coeruleus (LC). Withdrawal syndrome is temporally associated with hyperactivity of LC neurons. However, LC neurons do not show withdrawalinduced hyperactivity in the brain slices from morphine-dependent rats. Thus, it has been suggested that the increase in LC neuronal activity seen in vivo is mediated by extrinsic factors. Therefore, this study was carried out to find whether LC microinjection of orexin-A can induce withdrawal behaviors. Methods: Adult male Wistar rats weighing 250-300 grams were rendered morphine dependent by subcutaneous injection of morphine sulfate (10 mg/kg) at an interval of 12 h for 9 days. On day 10, intra-LC microinjection of orexin- A (100 μM, 200 nl) was performed two hours after morphine administration. Thereafter, somatic signs of withdrawal were evaluated in a Plexiglas chamber (30 cm diameter, 50 cm height) during a period of 25 min. Results: Orexin-A induced several signs of morphine withdrawal including chewing, scratching, rearing, teeth chattering, wet-dog shake and paw tremor. Acute LC microinjection of an orexin type 1 receptor antagonist, SB- 334867-A, prior to orexin-A prevents the expression of these signs. Conclusion: It may be concluded that orexin, via orexin type 1 receptor at LC acts as an extrinsic factor in the expression of morphine withdrawal syndrome.
Farzana Yadegari, Ali Heidarianpour, Farzad Nazem, ,
Volume 15, Issue 2 (8-2011)

Introduction: Nowadays Opioids are gaining acceptance for the management of moderate to severe and chronic pain. In addition, a number of studies have shown that plasma levels of β-endorphin (βEP) in exercise trained are higher than sedentary rats. In our study we assume that exercise training can reduce pain after withdrawal syndrome in morphine-dependent rats. Methods: Male Wistar rats (250±20 g, N=24) were addicted by morphine sulfate 0.4mg/ml (for 21 days) and animals were submitted to swimming training, five days a week for 8 weeks, in which First 60 minutes for 3 weeks and then 90 minutes in two weeks and at the end 120 min for 3weeks. At the end of each stage of exercise protocol naloxan hydrochloride (3mg/kg.ip) was injected. Tail-flick was used to assess the effect of training on nociceptive threshold. Results: Data showed that swimming aerobic exercise significantly increased pain threshold in trained control and addicted rats (p<0.05) while pain responses did not significantly change in sedentary control and addicted rats. Conclusion: Our results indicate that swimming training has analgesic property in morphine withdrawal-induced hyperalgesia in rats. Therefore, it can be used for the treatment and/or management of painful conditions.
Mahboubeh Kamali, Hedayat Sahraei, Maryam Khosravi, Shahin Hassanpour, Habib Yaribeygi,
Volume 19, Issue 4 (12-2015)

Introduction: Morphine withdrawal syndrome is mediated via several central and peripheral neurological pathways. In the present study we investigated the role of N-methyl-D aspartic acid (NMDA) glutamate receptor on naloxone-induced withdrawal syndrome in morphine-conditioned mice. Materials and Methods: We designed two separate experiments. In experiment one, 30 male NMRI mice were divided into 5 groups, pretreated with memantine (0.1, 1 and 5 mg/kg; I.P.) followed by morphine-dependence period for 3 days. In the other experiment, 48 male NMRI mice distributed into 8 groups, pretreated with intra-accumbens (IAc) memantine (1 and 5 μg/animal) within the right, left and both side of nucleus accumbens (RNAcc, LNAcc and BNAcc) followed by I.P. morphine-dependence (3 days). On day 4, in both experiments, morphine was injected into mice, followed by naloxone. Then naloxone-induced total jumping count, jump height and defecation in morphine-conditioned mice were recorded for 30 min. Results: Pre-treatment by I.P. injection of memantine significantly attenuated naloxone precipitated jumping count/30 min, jumping height (mm) and fecal material output in morphine dependent mice (P<0.05). Also, IAC pretreatment with memantine in LNAcc, RNAcc and BNAcc significantly declined the effect of I.P. injection of naloxone on total jumping count and jumping height (P<0.05), pretreatment within memantine in LNAcc, RNAcc and BNAcc had no effect on defecation (P>0.05). Conclusion: These findings indicated asymmetric involvement of central and peripheral NMDA glutamate receptors in withdrawal syndrome development in morphine-dependent mice.

Mahnaz Kesmati, Maryam Konani, Mozhhgan Torabi, Lotfollah Khajehpour,
Volume 20, Issue 3 (8-2016)

Introduction: Our previous study has showed that chronic administration of magnesium oxide nanoparticles (MgO NP) can reduce anxiety in adult male rat. In this study the effects of MgO NP on anxiety induced by morphine withdrawal were investigated in adult male mice. Methods: Adult male NMRI mice (weighing 27 ± 3 g) divided into groups: control, receiving intraperitoneal (i.p.) injection of MgO NP (1, 2.5, 5 mg/kg), morphine withdrawal groups that receiving saline or MgO NP (2.5, 5 &10 mg/kg) as acute (a single injection at the test day) and chronic (co-injected with morphine for 4 days). To develop morphine dependency, increasing doses of morphine (20, 40, 80 mg/kg( injected subcutaneously for 4 days. Mice received a final morphine injection (40 mg/kg) 3 hours prior to naloxone (5 mg/kg (i.p.) on the day of testing (day 4). In addicted groups, after naloxone injection, morphine withdrawal signs were evaluated. In all groups, anxiety like behavior was assessed by the elevated plus maze apparatus. Results: MgO NP (2.5 & 5 mg/kg) reduced anxiety like behavior (P<0.05). Acute and chronic MgO NP injections (5&10 mg/kg) could significantly improve/alleviate anxiety like behavior (p<0.05 & p<0.01 respectively) and reduce locomotor activity (p<0.05, acute; p<0.05, & p<0.01, chronic), rearing, climbing and weight loss in morphine withdrawn mice. Conclusion: Due to the positive effect of MgO NP on anxiety like behavior and morphine withdrawal signs and symptoms, this nanoparticle can be a potential candidate for reducing the side effects of chronic usage of morphine and morphine withdrawal.

Maryam Moghimian, Somaye Aalami, Seyed-Hosein Abtahi-Evari, Malihe Soltani,
Volume 22, Issue 2 (6-2018)

Introduction: To study the effect of withdrawal syndrome in morphine-dependent male rats. Methods: Adult male rats were divided randomly into four groups: control (G1), received morphine (G2), received morphine and treated by clove (G3) and only treated by clove (G4). The rats were administered increasing doses of morphine (0.1, 0.2 and 0.3 mg/ml), each dose being administered for two days, and then a dose of 4 mg/ml was given every day for 21 consecutive days. After the last oral dose of morphine on day 21, the rats were treated daily with oral clove (4 mg/ml/kg) for 14 days. Following the treatment, the histological parameters, oxidative stress, LH, FSH and testosterone levels were measured. Results: The histological parameters were not significantly changed. In the morphine group, it was observed that the levels of LH, FSH and testosterone decreased significantly in comparison to the control group and clove treatment could significantly increase the LH, FSH, testosterone, glutathione peroxidase and superoxide dismutase levels in G3 groups. Also, the level of malondialdehyde (MDA) increased significantly in the morphine group and treatment with clove could significantly decrease the MDA level in G3 groups. Conclusion: Our results showed that the hormone levels (LH, FSH and testosterone) and antioxidant enzyme increased with the administration of clove after morphine withdrawal. This may be because of the antioxidant effect of clove or the direct effect of this plant on the hypothalamic–pituitary–gonadal axis, or both.

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