Harmine exhibits anti-apoptotic properties and reduces diabetes-induced testicular damage caused by streptozotocin in rats.

Objective: Diabetes mellitus induces fertility problems in men, mainly because of increased free radicals. Natural resources are effective for male infertility treatment. This study investigated the effects of harmine, an alkaloid available in Peganum harmala L., on the male reproductive system of diabetic rats. Methods: We divided 32 rats into four groups, and eight were randomly placed in each group. For diabetes induction, the animals received 50 mg/kg of streptozotocin intraperitoneally. After 1 week, animals received 15 mg/kg of harmine (28 days; intraperitoneal). Histopathological examinations, serum levels of male hormones, levels of nitric oxide (NO) and malondialdehyde (MDA) in the testes, total antioxidant capacity (TAC), insulin serum levels, fasting blood glucose levels, the apoptotic index, and semen analysis were assessed. Results: The diabetes group exhibited morphological changes in testicular tissue, significant decreases in the diameter of the seminiferous tubule, the Johnsen score, testosterone, luteinizing hormone, follicle-stimulating hormone, insulin serum levels, and TAC in testicular tissue (p<0.01). Harmine treatment ameliorated the morphological changes in the testes and improved sperm parameters relative to the diabetes group (p<0.05). The NO and MDA levels in the testes, fasting blood glucose serum levels, and apoptotic index parameters were significantly elevated in the diabetes group, while in the diabetes+harmine group, these parameters were reduced (p<0.01). Conclusion: Harmine protects testicular tissue and sperm against diabetes-induced damage. This effect of harmine is associated with a rebalancing of the antioxidant capacity that subsequently decreases apoptosis in the testes.

Role of sex hormones in the effects of sleep deprivation on methamphetamine reward memory.

Sleep deficiency is known as an important risk factor for relapse to drug abuse, especially for the powerful psychostimulant methamphetamine (METH). On the other hand, both drug addiction and sleep neurobiology are affected by sex hormones. We, therefore, aimed to examine the probable effects of sleep deprivation (SD) on methamphetamine (METH) reward memory in male and female rats. Moreover, we asked if sex hormones influence the effects of SD on METH reward memory. Adult male and female Wistar rats were divided into two main groups, sham and gonadectomized groups. Three weeks later, they were conditioned to receive METH (2 mg/kg, i.p.) in the conditioned place preference. METH reward memory was then reinstated following a 10-day extinction period. SD was induced for 72 h, either before or after extinction, in different groups. In gonadectomized animals, they daily received either subcutaneous administration of estrogen (5 µg/0.1 ml oil) or progesterone (2 mg/0.1 ml oil) or dihydrotestosterone (25 mg/0.1 ml oil) for thirteen days, from post-conditioning day to reinstatement session. We found that SD facilitated relapse to METH reward memory, depending on the time interval between SD and METH reinstatement. Furthermore, we found that estrogen and SD showed synergistic effects to facilitate METH reward memory, whereas testosterone and progesterone revealed inhibitory effects in the controls, but not in the SD, animals. Our findings would seem to suggest that sex hormones should be considered as determinant factors to manage METH abuse and relapse to METH seeking/taking behavior, especially for those with sleep deficiency.

Role of Cannabinoid CB1 Receptor in Object Recognition Memory Impairment in Chronically Rapid Eye Movement Sleep-deprived Rats.

Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor (CB1R) could affect novel object recognition (NOR) memory in chronically rapid eye movement sleep-deprived (RSD) rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique. The CB1R antagonist rimonabant (1 or 3 mg/kg, i.p.) was administered either at one hour prior to the sample phase for acquisition, or immediately after the sample phase for consolidation, or at one hour before the test phase for retrieval of NOR memory. For the reconsolidation task, rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition, consolidation, and retrieval, but it did not affect the reconsolidation of NOR memory. Rimonabant administration did not affect acquisition, consolidation, and reconsolidation; however, it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings, along with our previous report, would seem to suggest that RSD may affect different phases of recognition memory based on its duration. Importantly, it seems that the CB1R may, at least in part, be involved in the adverse effects of chronic RSD on the retrieval, but not in the acquisition, consolidation, and reconsolidation, of NOR memory.

Maternal sleep deprivation affects extinction and reinstatement of methamphetamine reward memory in male offspring: Role of the D1-like and D2-like dopamine receptors.

Maternal sleep-deprivation (MSD) has been shown to induce stress, hyperactivity, and risk taking behavior in the offspring; howbeit, it is not yet clear whether it may also affect vulnerability to psychostimulant abuse in the offspring. We aimed to determine whether MSD affects extinction and reinstatement of methamphetamine (METH) reward memory in the offspring and also to evaluate the possible role of dopamine D1-like and D2-like receptors in these processes. Thirty-day-old male offspring born to control and sleep-deprived dams (during the third week of pregnancy) were trained to acquire METH-induced place preference (2 mg/kg., i.p.). METH reward memory was then reinstated following an 8-day period of extinction. The offspring received SCH 23390 (0.03 or 0.1 mg/kg, i.p.) or sulpiride (20 or 60 mg/kg, i.p.) as antagonists of dopamine D1-like and D2-like receptors, respectively, either immediately after each daily extinction session or prior to the reinstatement session. MSD postponed METH extinction and facilitated METH reinstatement in the offspring. SCH 23390 facilitated METH extinction and decreased reinstatement of the extinguished METH preference. Sulpiride in the offspring from sleep-deprived dams facilitated METH extinction, but it did not affect reinstatement of the extinguished METH reward memory. It seems that MSD may enhance vulnerability to METH abuse in the offspring. Furthermore, both dopamine D1-like and D2-like receptors may mediate METH extinction in the offspring born to the sleep-deprived dams; however, only the dopamine D1 receptor may play an important role in reinstating the extinguished METH reward memory in the offspring.

REM sleep deprivation before extinction or reinstatement alters methamphetamine reward memory via D1-like dopamine receptors.

We aimed to determine whether REM sleep deprivation (RSD) affects extinction and reinstatement of methamphetamine (METH) reward memory in male rats and also to evaluate the possible role of dopamine D1-like and D2-like dopamine (DA) receptors in these processes. Male rats were trained to acquire METH-induced place preference (2 mg/kg, i.p.). METH reward memory was then reinstated following a 10-day extinction period. The animals underwent a 72-hour sleep deprivation episode by multiple platforms method (in separate groups), either before the extraction or before the reinstatement of METH reward memory. The animals received SCH 23390 (0.01 or 0.05 mg/kg, i.p.) or sulpiride (20 or 60 mg/kg, i.p.) as antagonists of D1-like and D2-like DA receptors, respectively, either immediately following each daily extinction session or before the reinstatement of METH-seeking behavior. The RSD episode postponed extinction and facilitated reinstatement of METH reward memory. Administration of SCH 23390, but not sulpiride, facilitated METH extinction and decreased reinstatement of the extinguished METH-seeking behavior. Moreover, locomotor activity was not affected by METH and/or the RSD paradigm. The results would seem to suggest that the D1-like, but not the D2-like, DA receptors may be involved in the extinction and reinstatement of the extinguished METH reward memory in RSD animals. Nonetheless, more investigations are needed to elucidate the exact mechanisms involved.

Novel object recognition memory in REM sleep-deprived rats: Role of the cannabinoid CB1 receptor.

A survey of the literature indicates that both rapid eye movement sleep deprivation (RSD) and activation of cannabinoid CB1 receptor (CB1R) may impair novel object recognition (NOR) memory in rodents. To our knowledge, so far, no previous study has investigated the probable effects of RSD on the different phases of NOR memory. Moreover, far too little attention has been paid to the potential role of the CB1R in the effects of RSD on object memory. Therefore, the major objective of this study was to investigate the probable role of the CB1R in the acquisition, consolidation, retrieval, and reconsolidation of NOR memory in the RSD rats. A 12-h paradigm of RSD using the multiple platform method did not affect acquisition, but it impaired the consolidation, retrieval, and reconsolidation of NOR memory. Administration of the CB1R antagonist rimonabant (1 or 3 mg/kg, i.p.) did not have significant effects on the acquisition and reconsolidation, but it improved RSD-induced impairment of the consolidation and retrieval of object memory, especially at the dose of 3 mg/kg. In addition, the RSD paradigm did not affect the levels of plasma corticosterone as an important marker of stress in rat. The results revealed that RSD may have different effects on the different phases of NOR memory which may not be attributable to the effects of stress. Our findings would seem to suggest that the CB1R can be targeted to, at least partially, modulate the adverse effects of RSD on the process of NOR memory.

REM sleep deprivation impairs retrieval, but not reconsolidation, of methamphetamine reward memory in male rats.

Susceptibility to interference can be a result of memory retrieval and reconsolidation. Given the fact that addiction develops through the neural mechanisms of learning and memory, it would not be surprising that a consolidated drug reward memory may also be susceptible to interference following retrieval/reconsolidation. Due to the critical role of sleep in memory consolidation, sleep deprivation (SD) has been shown to impair memory. Therefore, the major objective of this study was to investigate the effect of rapid eye movement (REM) sleep deprivation (RSD) on the retrieval and reconsolidation of methamphetamine (METH) reward memory in male rats. The animals were trained to acquire METH-induced CPP (2 mg/kg, i.p.). METH reward memory was then reactivated/retrieved in the drug-paired chamber during a drug-free (memory reactivation) session. A period of 48-h RSD paradigm using the multiple platform technique resulted in persistent deficits in the retrieval of METH reward memory. Nevertheless, the same protocol of RSD, which was conducted immediately after the memory reactivation, did not affect the reconsolidation of METH reward memory. Additionally, the RSD episode induced a temporary potentiation of METH-induced hyperlocomotion. Our findings would seem to suggest that sleep is involved in the retrieval, but not reconsolidation, of METH reward memory. The results may also demonstrate that RSD mimics the effects of METH on locomotor activity. The results of this study, therefore, support the idea that sleep is involved in the processing of METH reward memory which can be considered for further investigations to manage the relapse associated with drug-related memory.

Naloxone Ameliorates Spatial Memory Deficits and Hyperthermia Induced by a Neurotoxic Methamphetamine Regimen in Male Rats.

BACKGROUND: Methamphetamine (METH) as a synthetic psychostimulant is being increasingly recognized as a worldwide problem, which may induce memory impairment. On the other hand, it is well established that naloxone, an opiate antagonist, has some beneficial effects on learning and memory. The present research aimed at evaluating naloxone effects on spatial learning and memory impairment triggered by a neurotoxic regimen of METH in male rats. MATERIALS AND METHODS: The animals received the subcutaneous (sc) regimen of METH (4×6 mg/kg at 2-h intervals), intraperitoneal (ip) naloxone (4×1 mg/kg at 2-h intervals), or normal saline at four events. The Nal-METH group of rats received four naloxone injections (1 mg/ kg, ip) 30 min before each METH injection (6 mg/kg, sc) at 2-h intervals. Seven days later, they were evaluated for spatial learning and memory in the Morris Water Maze (MWM) task. RESULTS: METH regimen induced hyperthermia, as well as a poor performance, in the acquisition and retention phases of the task, indicating spatial learning and memory impairment compared to the controls. Naloxone administration (1 mg/kg, ip) before each METH injection led to significant attenuations of both hyperthermia and METH adverse effects on the rat performance in the MWM task. CONCLUSION: The results revealed that pretreatment with the opiate antagonist naloxone could prevent METH adverse effects on body temperature and memory performance. It seems that the opioidergic system and hyperthermia may, at least partially, be involved in METH effects on spatial memory.

Sleep Architecture in Patients With Primary Snoring and Obstructive Sleep Apnea.

INTRODUCTION: This study aimed to investigate sleep architecture in patients with primary snoring and obstructive sleep apnea. METHODS: In this study, we analyzed polysomnographic data of 391 clients who referred to Sleep Disorders Research Center (SDRS). These people were classified into three groups based on their Apnea-Hypopnea Index (AHI) and snoring; control, Primary Snoring (PS), and Obstructive Sleep Apnea (OSA) group. Sleep architecture variables were then assessed in all groups. RESULTS: The results of this study indicated a decrease in deep sleep or Slow Waves Sleep (SWS) and increase in light sleep or stage 1 of non-REM sleep (N1) in OSA patients compared with the control and PS groups. After controlling the effects of confounding factors, i.e. age and Body Mass Index (BMI) (which was performed through multiple regression analysis) significant differences were observed among the three groups with regard to N1. However, with regard to SWS, after controlling confounding variables (age and BMI), no significant difference was found among the groups. CONCLUSION: The results indicated that OSA, regardless of age and BMI, may increase light (N1) sleep possibly via a decline in blood oxygen saturation (SpO2 ). Such increase in N1 may be responsible for brain arousal. In addition, by controlling confounding factors (age and BMI), OSA did not affect SWS in OSA patients. However, further research is necessary to determine sleep architecture in more detail in the patients with OSA.

The role of local renin-angiotensin system on high glucose-induced cell toxicity, apoptosis and reactive oxygen species production in PC12 cells.

OBJECTIVES: Hyperglycemia, oxidative stress and apoptosis have key roles in pathogenesis of diabetic neuropathy. There are local renin-angiotensin systems (RASs) in different tissues such as neural tissue. Local RASs are involved in physiological and pathophysiological processes such as inflammation, proliferation and apoptosis. This study aimed to investigate the role of local renin-angiotensin system on high glucose-induced cell toxicity, apoptosis and reactive oxygen species (ROS) production in PC12 cells, as a cell model of diabetic neuropathy. MATERIALS AND METHODS: PC12 cells were exposed to a high glucose concentration (27 mg/ml), captopril (ACE inhibitor), telmisartan and losartan (AT1 antagonists), and also PD123319 (AT2 antagonist) were administered before and after induction of high glucose toxicity. Then cell viability was assessed by MTT assay and apoptotic cells and intracellular ROS production were detected by annexin V-propidium iodide and DCFDA, respectively, using flow cytometry. RESULTS: High glucose concentration decreased cell viability, and increased apoptotic cells. Intracellular ROS production was also increased. In PC12 cells pretreatment and treatment by the drugs showed a significant improvement in cell viability and reduced apoptosis in captopril, telmisartan and PD123319 but only captopril and telmisartan were able to reduce ROS production. Losrtan significantly lowered ROS but didn't show any improvements in cell viability and apoptotic cells. CONCLUSION: The results of the present study showed that RAS inhibitors reduced cell toxicity and apoptosis and ROS production was induced by high glucose. It may be suggested that local RAS has a role in high glucose toxicity.

The effects of aqueous extract of Aloe vera leaves on the gastric acid secretion and brain and intestinal water content following acetic acid- induced gastric ulcer in male rats.

OBJECTIVE: Gut-brain axis (GBA) is very important in creation and modulation of gastrointestinal problems. Aloe vera gel has gastroprotective properties. The purpose of this study was to evaluate the effect of aqueous extract of Aloe vera leaves on the gastric acid secretion and brain and intestinal water content following acetic acid gastric ulcer induction. MATERIALS AND METHODS: Gastric ulcer was induced by injection of 20% acetic acid into the subserosal layer in male rats. Rats were randomly assigned into three groups: intact group, gastric ulcer group and Aloe vera group (treatment with Aloe vera following gastric ulcer induction). The acid levels and brain and intestinal water content of each sample were measured eight days after the gastric ulcer induction. RESULTS: Gastric acid levels were significantly decreased in Aloe vera group when compared with gastric ulcer group (p<0.05). However, there were no differences in acid output between gastric ulcer and Aloe vera groups with intact group. After Aloe vera administration, the amount of brain water content had no difference with intact and gastric ulcer groups (p<0.05). The duodenal water content in Aloe vera group was significantly reduced compared with intact group (p<0.05) but gastric ulcer group had no significant difference with intact and Aloe vera group. CONCLUSIONS: The administration of Aloe vera has an inhibitory effect on the gastric acid output.