Clonidine an alpha-2 adrenergic agonist besides being used as antihypertensive, also causes analgesia and antagonizes the opiate withdrawal syndrome. Clonidine pretreatment in morphine dependent rats reduced the frequency of precipitated shakes but potentiated the frequency of escape attempts during naloxone induced withdrawal. Piloetection and excitement were also potentiated by clonidine pretreatment. The purpose of this study was to ascertain whether or not potentiation of some withdrawal signs by clonidine is mediated by alpha-1 adrenoceptors activation. To produce morphine dependence, morphine hydrochloride was added to drinking water. Morphine solution was prepared each day and the concentration was increased in two days interval. The abstinence syndrome was precipitated by injecting naloxone (3 mg/kg i.p). Clonidine and for prasosin were administered i.p. 10 and 20 minutes before naloxone, respectively. Some of withdrawal signs including escape attempts and precipitated shakes were counted during a fifteen minutes period after naloxone. Clonidine (0.5 and 1 mg/kg) reduced most of the withdrawal sings, but in a dose dependent manner, the drug potentiates the number of escape attempts that was in agreement with previous studies. In morphine dependent rats, prazosin pretreatment (0.1 and 0.4 mg/kg) did not affect any of the withdrawal sings except piloerection Co-administration of prazosin with clonidine in all doses significantly decreased the number of escape attempts in comparison with clonidine pretreated group. Furthermore, prazosin inhibited piloerection, another sign of withdrawal that was potentiated by clonidine. This study indicates the involvement of alpha-1 adrenoceptors in some of morphine withdrawal sings and potentiation of these signs during clonidine treatment.  

Background and Objective: Exposure to a stressor generates a wide variety of adaptive responses and alters the pharmacological effects of opioids. Common neural pathways are activated by morphine and stress. This study was done to determine the effect of chronic restraint stress and acute water immersion stress on the severity of naloxone precipitated morphine withdrawal manifestation in morphine-dependent rats.Methods: In this experimental study, 32 adult male Wistar rats were allocated into four groups equally including: morphine-dependent - no chronic restraint stress (D/NS) (Control), morphine-dependent with chronic restraint stress (D/R), morphine-dependent with acute water immersion stress (D/WI) and morphine-dependent with chronic restraint stress under acute water immersion stress (D/R+WI). Rats were injected with bi-daily doses (10 mg/kg/bw, sc, at 12h intervals) of morphine over a period of 10 days in the presence or absence of restraint stress (1 h/day). On day 11, immediately after naloxone hydrochloride injection (2mg/kg/bw, ip), withdrawal manifestation were recorded. Water immersion stress was performed prior to naloxone injection in D/WI and D/R+WI groups.Results: The overall score of morphine withdrawal was significantly lower in D/RS and D/RS+WI rats in compared to controls (P<0.05). Among the graded signs, the mean number of abdominal contractions and jumps was reduced in D/RS+WI and D/RS rats in compared to control groups (P<0.05). Among the checked signs, the number of rats per group with erection and genital grooming were reduced in restraint rats by 25% than control group (P<0.05).Conclusion: Chronic restraint stress with or no acute water immersion stress diminished severity of dependency on morphine. Thus, restraint stress may be applied as a method to ameliorate some of the withdrawal behavioural consequences of morphine.

Background: Many studies have showed that electromagnetic fields decreased WSSM. in this study the Objectives: effect of electromagnetic fields on WSSM is investigated on rats.Materials and methods: 102 male rats with weight (225-25) gr were classified in 17 groups (n=6). They were addicted by morphine injection according to Pinelli Method. 16 groups of them exposed to electromagnetic fields with 25, 50, 75 and 100 Hz frequency and with magnetic field 0/5, 1/5, 2/5 and 3/5 G intenscity. One group was chosen as control. 1) awiniWSSM in jumping, climbing, rearing, diarrhea, weight loss, ptosis by naloxan injection (5mg/kg/Ip) at all animals were investigated.Resalles: WSSM were obtained by counting the jumping, yawing, climbing, rearing. And the amoul of weinwt 1366 the ptosis, diarrhea were scord from +1 to +4.Conclusion: This study showed that magnetic fields caused the significant decreased on wawing, ptosis, weight loss and diarrhea at all of the exposure groups (P<0.001). Rearing and alimbing decrease significantly in groups that exposed to electromagnetic fields and this fields with 25 Hz frequency and 0/5 G intensity have minimum and with 100 and 75 Hz frequency and 3.5 G intensity have maximum effects on WSSM.

Background: Curcumin has anti-inflammatory and antinociceptive effects and also it can be exploited for drug abuse treatment, but its low bioavailability and water solubility are the most important obstacles and limit its application. The recent achievements of nanotechnology illustrate a novel approach in treatment of drug abuse and addiction. The present study was conducted to investigate the effect of dendrosomal Nano curcumin (DNC) administration on morphine withdrawal signs in rats. Methods: Male rats (250-300 gr) were anaesthetized and implanted with silastic catheters inserted into the right jugular vein. Then they were placed in the self-administration apparatus for 2 hours/day for 12 days and received saline or morphine (5mg/ml) by infusion pump. In addition, DNC (10, 5 mg/kg. IP) were injected 30 minutes before placing in apparatus and the signs of withdrawal were measured for 30 minutes after injection of naloxone (2 mg/kg, i. p). Results: Morphine significantly induced dependence and withdrawal signs in sham group. On the other hand injection of DNC significantly decreases these signs (p<0/05). Conclusion: DNC can decrease withdrawal signs of morphine and can be used as an effective pharmacotherapy for morphine abuse.

Aloe vera is a herbal medicine for skin therapeutical objects. Many products like pomade, cream, gel, and shampoo for skin injuries have been made from this plant. Sometimes, the powder of this plant has also been used by mothers to keep out their infants from breast-feeding. In some of the books, this plant has been introduced as an opioid–receptors antagonist. In this study, 30 male mice (45-50 g) were randomly selected and divided into 5 groups (n=6). All of them received morphine sulphate (120 mg/kg, s.c., 3 times daily) for 3 days. Control group only received morphine. Treated-groups received Aloe vera (5, 10, 20 mg/kg, IP) and morphine daily for 3 days. clonidine group received clonidine (3 mg/kg, IP) and morphine daily for 3 days. At the end of session (4th day), all of the groups received naloxone (5 mg/kg, IP) and, then morphine withdrawal signs (jumping, climbing, diarrhea) were studied for 30 minutes. Our results show that 10 mg/kg of Aloe vera is the most effective dose for treatment of morphine withdrawal signs, especially for reduction of diarrhea and its effect on diarrhea was better that clonidine effect.

It has been shown that swimming stress and glucocorticoid injection significantly decrease the withdrawal syndrome signs of opioids in mice. In the current study, the effect of restraint stress on withdrawal syndrome signs was investigated in morphine-dependent mice. The experimental strategy of this study was performed on four groups of randomly divided rats;i.e., group A, which received normal saline (negative control), group B receiving morphine (positive control), group C, which received morphine after stress, and group D, which received morphine and stress at the same time. Animals in groups C and D were kept in restrainer for 7 consecutive days (4h/day). Data were subjected to the t test and one-way ANOVA and followed by Tukey test for multiple comparisons. The results showed that a significant reduction in stool weight occur in group D (0.48 ± 0.12 g) in comparison with group B (1.14 ±.0.23 g) respectively (p<0.05). However, no significant change in stool weight was observed comparing groups B and C. In addition, no significant change was observed in the number of jumping among groups B, C, and D.It can be concluded that restraint stress exerts short-term inhibitory effect on morphine action in gastrointestinal tract. The mechanism (s) underling this phenomenon remains to be elucidated.

Background and Purpose: Glutamatergic system has a role on morphine withdrawal sign, and magnesium has inhibitory effect on the NMDA receptors of glutamatergic system. The present study aimed to determine the effects of magnesium injection on morphine withdrawal signs in male and female rats.Materials and Methods: In this experimental study, 48 Male and female rats (200-250 gr) were used. The animals divided into 6 equal groups: two male and female control groups received normal saline; two male and female groups receiving magnesium sulfate 150 mg/kg; and the last two groups receiving magnesium sulfate 300 mg/kg. All groups received 3% sucrose in tap water with morphine 0.4mg/ml (for 21 days) to become addicted. In the end of 21st day, NS or magnesium administrated 30 min before naloxone (2mg/kg) and then withdrawal signs evaluated for next 30 min. The obtained data were analyzed in SPSS using ANOVA and complementary tests with p<0.05 as significant.Results: The results of this study showed that the injection of magnesium in dose of 150 mg/kg could significantly reduce many withdrawal symptoms in male addicted rats [Jumping 62.96% (2.5±1.14), standing 45.4% (6.62±1.45)] and in female addicted rats [Jumping 77.75% (1.25±0.54), climbing 24.51% (8.87±1.65), standing 52.57% (5.57±1.26)]. The injection of magnesium with dose of 300 mg/kg also reduced dramatically withdrawal symptoms in male rats [Jumping 87.03% (6.75±1.66), climbing 34.34% (12.87±1.27), standing 56.12% (12.125±1.27)] and female rats [Jumping 84.43% (0.875±0.25), climbing 36.17% (7.5±1.08), standing 69.07 % (3.75±0.64)].The administration of magnesium in both doses caused a significant reduction of most withdrawal symptoms, and its effect on both sexes was almost similar.Conclusions: It seems that the injection of magnesium during morphine withdrawal can considerably reduce the symptoms of withdrawal syndrome in rats.

Background: The opioid withdrawal syndrome can vary greatly in intensity. Depression is proposed to be one of the contributing factors in withdrawal intensity of opioid dependents. Methods: Fifty-one male heroin dependents were enrolled in this study. All of them were admitted to Beheshti Psychiatric Hospital in Kerman, Iran for detoxification of heroin dependence. Existence of depression was evaluated by means of Beck Depression Inventory (BDI), and DSM IV criteria for major depressive disorders before the start of withdrawal complaints. The opiate withdrawal questionnaire was used for evaluating withdrawal signs and symptoms, 24 and 72 hours after the start of withdrawal. Results: The mean age of subjects was 33.67 ± 8.36 years. By means of BDI, 28 (54.9%) and by means of DSM IV criteria 11 (21.57%) subjects were ranked as depressed. Scores of withdrawal signs and symptoms were higher in the depressed patients, 24 hours after beginning of withdrawal, but were only higher in patients with major depressive disorder 72 hours after the start of withdrawal. Conclusion: Existence of depression, especially in the form of major depressive disorder, could intensify withdrawal signs and symptoms. This should be taken into account by the treating physicians, during the detoxification period and further treatment plans.