Introducing a noninvasive, non-surgical, and reversible animal model for fecal incontinence using abobotulinumtoxinA in dogs.

The aim of this study was to introduce a new animal model of fecal incontinence (FI) by injecting abobotulinumtoxinA in the external anal sphincter (EAS) muscle of dogs which replaces models based on anal sphincter destructions that are invasive, mostly require surgical procedures, expensive, permanent, and painful to the animals. 4 healthy mongrel dogs were used in this study. First, they were received NaCl 0.09% (as control) injections in EAS muscle and effects were assessed by means of Electromyography (EMG) and clinically evaluated by sphincter pinch test and presence of leakage of feces for 2 weeks. Then, they received abobotulinumtoxinA in EAS muscle and reevaluated for 6 weeks to see short-term and medium-term effects of abobotulinumtoxinA injection. Saline had no significant changes in results obtained from EMG, however, there were significant decreases in amplitudes of action potentials after receiving abobotulinumtoxinA in comparison with no injection or saline injection in EAS muscle. Pinch tests were normal after saline injection assessment period, however, then started to be negative, ranging from two days after abobotulinumtoxinA injection to seven days after receiving abobotulinumtoxinA. Animals also had significant presentations of fecal incontinence (leakage of feces and cage contamination with feces) from the 1st week after receiving abobotulinumtoxinA until the 6th week after receiving abobotulinumtoxinA. AbobotulinumtoxinA caused paralysis in the EAS and producd FI conditions in dogs. This animal model was an appropriate substitute to the various invasive, expensive and also complicated procedures with an easy, feasible, noninvasive and non-painful single-stage abobotulinumtoxinA injection.

Study of the effects of controlled morphine administration for treatment of anxiety, depression and cognition impairment in morphine-addicted rats.

BACKGROUND: Morphine dependency usually results in undesired outcomes such as anxiety, depression, and cognitive alterations. In this study, morphine was used to manage morphine dependence-induced anxiety, depression, and learning and memory disturbances. MATERIALS AND METHODS: Forty rats were divided equally into five groups. Group 1 received saline for 21 days. Groups 2-5 were dependent by increasing administration of morphine (15-45 mg/kg) for 7 days. For the next 14 days, morphine was administered as the following regimen: Group 2: once daily; 45 mg/kg (positive controls), Group 3: the same dose with an increasing interval (6 h longer than the previous intervals each time), Group 4: the same dose with an irregular intervals (12, 24, 36 h intervals interchangeably), and Group 5: decreasing doses once daily (every time 2.5 mg/kg less than the former dosage). On days 22-26, elevated plus maze (EPM), open field test (OFT), forced swim test (FST), and tail suspension test (TST) were performed to investigate anxiety level and depression in animals. Between 17th and 21st days, Morris water maze (MWM) was used to evaluate the spatial learning and memory. RESULTS: Chronic morphine administration caused depression and anxiety as observed by FST, EPM, and TST and decreased motor activity in OFT and caused impairment in learning and memory performance in MWM. Treatment with our protocol as increasing interval, irregular interval, and decreasing dosage of morphine caused marked reduction in depression, anxiety, and improved cognition performance compared with positive control group; and attenuated motor deficits in morphine-dependent rats, remarkably. CONCLUSIONS: Change in dosage regimens of morphine can reduce morphine-induced anxiety, depression, and cognitive impairments.

Attenuation of alcohol withdrawal syndrome and blood cortisol level with forced exercise in comparison with diazepam.

Relieving withdrawal and post-abstinence syndrome of alcoholism is one of the major strategies in the treatment of alcohol addicted patients. Diazepam, chlordiazepoxide, and topiramate are the approved medications that were used for this object. To assess the role of non-pharmacologic therapy in the management of alcohol withdrawal syndrome, we analyzed effects of forced exercise by treadmill on alcohol dependent mice as an animal model. A total of 60 adult male mice were divided into 5 groups, from which 4 groups became dependent to alcohol (2 g/kg/day) for 15 days. From day 16, treatment groups were treated by diazepam (0.5mg/kg), forced exercise, and diazepam (0.5 mg/kg) concurrent with forced exercise for two weeks; And the positive control group received same dose of alcohol (2 g/kg/day) for two weeks. The negative control group received normal saline for four weeks. Finally, on day 31, all animals were observed for withdrawal signs, and Alcohol Total Withdrawal Score (ATWS) was determined. Blood cortisol levels were measured in non-fasting situations as well. Present findings showed that ATWS significantly decrease in all treatment groups in comparison with positive control group (P<0.05 for groups received diazepam and treated by forced exercise and P<0.001 for group under treatment diazepam + forced exercise). Moreover, blood cortisol level significantly decreased in all treatment groups (P<0.001). This study suggested that forced exercise and physical activity can be useful as adjunct therapy in alcoholism and can ameliorate side effects and stress situation of withdrawal syndrome periods.

Attenuation of morphine withdrawal syndrome by various dosages of curcumin in comparison with clonidine in mouse: possible mechanism.

BACKGROUND: Herbal medical compounds and their major constituent have been used in the management and treatment of opioid withdrawal syndrome and pain. This study was carried out to clarify the effect of curcumin, the major compound of turmeric, on morphine withdrawal syndrome in mouse model and its possible mechanisms of pain relieving activity by assessing in writhing test as a model of visceral pain. METHODS: Due to two separate protocols (withdrawal syndrome and pain), 144 male albino mice were divided in two major groups. In withdrawal syndrome group, test effect of various dosages of curcumin (10, 20, and 40 mg/kg) was assessed on withdrawal signs and compared with positive and negative control and standard treatment (clonidine 0.4 mg/kg) groups. In pain groups, to determine the mechanism of pain relieving activity of curcumin, various dosages of curcumin (10, 20, and 40 mg/kg) in three separated groups, were used against acetic acid induced writhing (which is a constriction) test. The most effective dose (40 mg/kg) was used in writhing test and compared with groups pretreated with antagonist of major neurotransmitters involved in pain; and compared with group pretreated with vehicle (DMSO, 0.05%) as control. RESULTS: Curcumin attenuates withdrawal syndrome in a dose dependent manner in comparison with the dependent positive control group (P<0.05). It also indicated that pretreatment with naloxone and cyproheptadine significantly attenuate antinociception effect of curcumin (P<0.05). CONCLUSION: This study advocate that antinociception of curcumin was mediated by opioidergic and adrenergic system.

Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats.

BACKGROUND: Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. MATERIALS AND METHODS: Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25(th) day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20(th) and 25(th) days. RESULTS: The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment results in the nicotine withdrawal period (P < 0.05). CONCLUSION: This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.