The Effects of Chronic Marijuana Administration on 6-OHDA-Induced Learning & Memory Impairment and Hippocampal Dopamine and Cannabinoid Receptors Interaction in Male Rats.

There are general inhibitory effects of exo-cannabinoids on dopamine-mediated behaviors. Many studies suggested the interaction between cannabinoid receptors and dopamine receptors in the brain that affect cognition behaviors. In this paper, we investigate the effects of marijuana on 6-OHDA-induced cognitive impairments and the expression of dopamine and cannabinoid receptors in the hippocampus of male rats. 42 rats were divided into six groups. 6-hydroxy dopamine (6-OHDA) was administrated into the substantia nigra. Marijuana (60 mg/kg; i.p.) was administered 28 days, one week after the 6-OHDA injection. Morris water maze (MWM) and novel object recognition tests were performed. The hippocampal expression levels of cannabinoid receptors and D1 and D2 dopamine receptors evaluate by real-time PCR. The results showed marijuana improved the spatial learning and memory disorders caused by 6-OHDA in the MVM task and novel object recognition test. Additionally, the level of both D1 and D2 mRNA was decreased in 6-OHDA-treated animals and marijuana consumption only increased the hippocampal level of D1 mRNA. Moreover, the level of hippocampal CB1 mRNA in 6-OHDA- treated rats was higher than in control rats. However, the hippocampal level of CB2 mRNA was decreased in 6-OHDA- treated rats. Marijuana consumption caused a significant decrease in CB1 mRNA level and an increase in CB2 mRNA level in 6-OHDA + marijuana group. Therefore, marijuana may be helpful for learning & memory disorders, D1, and D2 dopamine receptors, and cannabinoid receptor alteration in patients with Parkinson's disease.

The effects of a new antidiabetic glycinium [(pyridine-2, 6-dicarboxylato) oxovanadate (V)] complex in high-fat diet of streptozotocin-induced diabetic rats.

OBJECTIVE: The present study aimed to evaluate the antidiabetic effects of glycinium [(pyridine-2, 6-dicarboxylato) oxovanadate (V)] complex in type 2 diabetes rat model. MATERIALS AND METHODS: Rats were allocated into 6 groups. Group I, nondiabetic rats; Group II, diabetic rats; Group III, diabetic rats receiving an intraperitoneal (i.p.) injection of metformin (45 mg/kg); Groups IV, V and VI were diabetic rats receiving i.p. injection of 5, 10, and 20 mg/kg of the complex for 3 weeks, respectively. Fasting blood glucose (FBG), insulin, liver enzymes, malondialdehyde (MDA), total antioxidant capacity (TAC), lipid profile, and HbA1c were measured. RESULTS: AST, ALT and GGT activities and MDA levels were increased, while TAC was decreased in diabetic animals. Treatment of diabetic rats improved the HOMA-IR and returned HbA1c level to the normal value as well as elevated TAC and reduced MDA level. CONCLUSION: We found that the complex possesses antidiabetic properties in experimental diabetes.

The different role of G-protein-coupled receptor 30 (GPR30) in the interaction effects of marijuana and estradiol on spatial learning and memory at different ages.

Some studies suggest that the effect of cannabis on behavior performance depends on the presence of ovarian hormones and the age of use initiation. Estradiol is the main ovarian hormone that can interact with cannabinoids. It has been suggested that cannabinoids exert some of their effects directly through estrogen receptors (ERs). A novel G-protein-coupled receptor (GPR30) was described as mediating estrogen signaling in various cell lines. Since there are few studies on the interaction of cannabis and ovarian hormones on cognitive behaviors, so, this study evaluated the role of GPR30 in the effects of marijuana (M) and estrogen, alone and in combination, on spatial learning and memory of young (non-ovarian(OVX)) and old female rats. Young (5-7 months) and old (22-24 months) female rats received an intraperitoneal injection (i.p) of 17ß-estradiol (E2), G1 (GPR30 agonist), and G15 (GPR30 antagonist) every four days, and M (every day), either alone or in combination, for 28 days. One hour after the last injection, the Morris water maze (MWM) test was conducted to evaluate of spatial learning and memory. Moreover, hippocampal BDNF level was assessed by the ELISA method. The results showed a positive effect of M on spatial learning in both young and old rats, however, E2 showed beneficial effects on the memory of young, but not old rats. Our results showed that GPR30 does not have any role in the interaction effects of M and E2 in young rats. Although both E2 and M alone showed positive effects on spatial learning and memory in old rats, however, our results showed a negative interaction between marijuana and E2 combined effects on spatial learning and memory in old female rats which is mediated by GPR30. Our results showed that the effects of GPR30 on spatial learning and memory is age dependent. Furthermore, this study showed that hippocampal BDNF does not have any role in the interaction effects of M and E2 on spatial learning and memory in young and old rats.

The effects of gallic acid and metformin on male reproductive dysfunction in diabetic mice induced by methylglyoxal: An experimental study.

BACKGROUND: Diabetes mellitus is a disease that has reached a dangerous point. Today, nearly 500 million men and women around the world live with diabetes. Gallic acid (Gal) affects diabetes. OBJECTIVE: To evaluate the effects of Gal and metformin (met) on the levels of glucose, insulin, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sperm count, antioxidant status, and histological changes in the testes of diabetic mice induced by methylglyoxal (MGO). MATERIALS AND METHODS: In this experimental study, 50 male adult NMRI mice, weighting 25-30 gr, aged 3-4 months were randomly divided into five equal groups (n = 10/each). (i) Control (vehicle, normal saline), (ii) MGO (600 mg/kg/d) orally for 28 days, (iii) Gal (50 mg/kg/d), (iv) MGO+Gal, and (v) MGO+met (200 mg/kg/d). Gal and met were administered orally for 21 consecutive days after the induction of diabetes. Blood samples were taken at 24 hr after the latest doses of treatment. Histological assessment of the testis was done, and the epididymis sperm count was obtained. Antioxidant indices, glucose, insulin, LH, FSH, and testosterone levels were measured. RESULTS: In the MGO group compared to the control group, insulin, glucose (p = 0.001), LH (p = 0.04) and malondialdehyde (p = 0.001) were increased. However, the level of testosterone (p = 0.001), seminiferous tubule diameters, epithelial height, sperm count, superoxide dismutase activity (p = 0.02), and testis volume (p = 0.01) were decreased. The results indicated that Gal and met ameliorated the MGO effects. CONCLUSION: These findings suggested that the animals receiving MGO became diabetic. According to the results, Gal and met can effectively prevent MGO-induced diabetes. The effect of Gal was equivalent and sometimes better than metformin.

Marijuana and ß-estradiol interactions on spatial learning and memory in young female rats: Lack of role of the G protein-coupled estrogen receptor (GPR30).

It has been shown that 17ß-estradiol (E2) hormone is an essential biological factor for increasing the sensitivity of women to drug abuse. Recent studies have shown a potential overlap between the molecular pathways of cannabinoids and ovarian hormones. The current study evaluated the interference between the marijuana and E2 effect on spatial learning and memory and the role of the G protein-coupled estrogen receptor (GPR30) in young female rats. The animals were separated into two main groups: intact-ovary and ovariectomized (OVX) rats. The latter group received intraperitoneal injections of E2, G-1 (GPR30 agonist), G-15 (GPR30 antagonist), marijuana, and different combinations of these substances for 28 days. Spatial learning and memory were evaluated by the Morris water maze (MWM) test. We also assessed the BDNF (brain-derived neurotrophic factor) concentration and the hippocampal level of GPR30. The results showed a significant reduction of spatial learning and memory in OVX rats compared to intact-ovary rats, which were restored by E2 replacement. Moreover, treatment with G-1 mimicked E2 effects on spatial learning and memory. Marijuana impaired spatial learning and memory in intact-ovary rats, while improved in OVX rats. We also found that treatment with M + E2 induced significant impairment in spatial learning and memory; however, treatment with M + G1 and M + G15 + E2 showed no significant difference. No significant differences in BDNF expression were observed in experimental groups. These results suggest that marijuana and E2 interact in their effect on spatial learning and memory in young female rats, but GPR30 seems to play no role in this interaction.

Marijuana improved motor impairments and changes in synaptic plasticity-related molecules in the striatum in 6-OHDA-treated rats.

Using marijuana has become popular and is allowed for medical purposes in some countries. The effect of marijuana on Parkinson's disease is controversial and Medical marijuana may benefit for motor and non-motor symptoms of patients with Parkinson's disease. No research has been conducted to fully prove the benefits, risks, and uses of marijuana as a treatment for patients with Parkinson's disease. In the present study, several different approaches, including behavioral measures and the western blot method for protein level assay, were used to investigate whether exposure to marijuana affects the motor and synaptic plasticity impairment induced by 6-OHDA. Marijuana consumption significantly decreased apomorphine-induced contralateral rotation, beam travel time, beam freeze time, and catalepsy time, but significantly increased latency to fall in the rotarod test, balance time, and protein level of PSD-95 and dopamine receptor D1 in the 6-OHDA + marijuana group. These results suggest that marijuana may be helpful for motor disorders and synaptic changes in patients with Parkinson's disease.

The neuroprotective effects of hydro-alcoholic extract of olive (Olea europaea L.) leaf on rotenone-induced Parkinson's disease in rat.

Parkinson's disease (PD) is an age-related disease in which dopaminergic neurons in the nigrostriatal pathway are destroyed, resulting in movement and behavioral problems. Oxidative stress and the generation of reactive oxygen species play key roles in neurodegenerative diseases, such as PD. Rotenone (ROT) is a common pesticide that induces oxidative stress. Olive leaves extract (OLE) has antioxidant and neuroprotective effects. Thus, the aim of this study was to investigate the neuroprotective effects of OLE on ROT-induced oxidative stress in the midbrain of a rat model of PD. Ninety-six Wistar rats were randomly divided into the following 6 groups (n = 16 rats/group): Control, Sham, ROT, and 3 ROT + OLE (75, 150, and 300 mg/kg/daily) groups. ROT (2.5 mg/kg/48 h) was injected subcutaneously, and vehicle or OLE was orally administered for 30 days. The animals were then sacrificed, and their brains were removed. Biochemical measures, including the levels of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA), and the number of tyrosine hydroxylase (TH)-positive neurons were determined, and behavioral (rotarod and hanging) tests were conducted. The balance and muscle strength of the OLE (150 and 300 mg/kg)-treated groups were significantly improved. Treatment with OLE prevented the increases in the levels of MDA, significantly improved the SOD, CAT, and GPx levels in the midbrain, and prevented the depletion of the TH-positive neurons. These findings suggested that OLE has neuroprotective properties and that it might be useful for preventing the death of dopaminergic neurons in patients with PD.

Evaluation of Antidiabetic and Antihyperlipidemic Effects of Peganum harmala Seeds in Diabetic Rats.

The present study was carried out to investigate the antidiabetic and antihyperlipidemic properties of hydroalcoholic extract of Peganum harmala in streptozotocin-induced diabetic male rats. In an experimental study, 64 normal Wistar albino male rats (200-230 g) were randomly divided into 8 groups. Control and diabetic rats were treated with normal saline and three different doses (30, 60, and 120 mg/kg) of hydroalcoholic extract of Peganum harmala seeds for 4 weeks orally. At the end of treatment, blood samples were taken and glucose, triglycerides, total cholesterol, LDL-c, HDL-c, malondialdehyde (MDA), total antioxidant capacity (TCA), ALT, AST, GGT, bilirubin, and glycosylated hemoglobin (HbA1C) were determined. STZ-induced diabetic rats showed significant changes in the values of glucose, triglycerides, total cholesterol, LDL-c, MDA, TAC, ALT, AST, GGT, bilirubin, and HbA1C in comparison with normal rats. Administration of the extract to diabetic rats resulted in a remarkable decrease in glucose, lipid profiles, MDA, ALT, AST, GGT, bilirubin, and HbA1C levels and increase in TAC relative to diabetic group. The results of this study indicated that hydroalcoholic extract of Peganum harmala seeds possesses antidiabetic and hypolipidemic activities and could be useful in treatment of diabetes.

Ginger (Zingiber officinale Roscoe) prevents the development of morphine analgesic tolerance and physical dependence in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginger (Zingiber officinale Roscoe), a well-known spice plant, has been used traditionally in the treatment of a wide variety of ailments such as opiates withdrawal-induced disorders. However, its influences on opioid tolerance and dependence have not yet been clarified. MATERIALS AND METHODS: Adult male Wistar rats were rendered tolerant to analgesic effect of morphine by injection of morphine (10 mg/kg, i.p.) twice daily for 8 days. To develop morphine dependence, rats given escalating doses of chronic morphine. To determine the effect of ginger on the development of morphine tolerance and dependence, different doses of ginger were administrated before morphine. The tail-flick and naloxone precipitation tests were used to assess the degree of tolerance and dependence, respectively. RESULTS: Our results showed that chronic morphine-injected rats displayed tolerance to the analgesic effect of morphine as well as morphine dependence. Ginger (50 and 100 mg/kg) completely prevented the development of morphine tolerance. In addition, concomitant treatment of morphine with 100 and 150 mg/kg attenuated almost all of the naloxone-induced withdrawal sings which include weight lose, abdominal contraction, diarrhea, petosis, teeth chattering, and jumping. In addition, morphine-induced L-type calcium channel over-expression in spinal cord was reversed by 100 mg/kg ginger. CONCLUSION: The data indicate that ginger extract has a potential anti-tolerant/anti-dependence property against chronic usage of morphine.

Studying the effects of mobile phone waves on electro cardiogram parameters of students in zahedan university of medical sciences.

BACKGROUND: The increasing use of mobile phones in recent years has caused concerns about the effects of electromagnetic waves of mobile phonesonhuman biological processes. OBJECTIVES: This study was conducted in order to survey the effects of mobile electromagnetic waves on electro cardiogram parameters as heart rate, TP segment, PR interval, Time of QRS and T waves, and voltage of R wave. PATIENTS AND METHODS: In this quasi experimental study, 40 students, of Zahedan medical science University, 20 boys and 20 girls, who had referred to the laboratory of physiology were selected. At first a normal electro cardiogram in lead I was recorded for each of the subjects for 20 seconds. Then a mobile phone was placed near their body and while mobile was ringing and talking two other electrocardiograms were recording for 20 seconds. Electro cardiograms were recorded with power lab device and analyzed by chart 5 software. Finally an ANOVA was employed to analyze the data through the SPSS 17, followed by a Tukey test. RESULTS: There was significant difference between heart rate during talking in comparison with heart rate during ringing and resting in both genders. There was a significant decrease of resting TP segment in comparison with TP segment during ringing and talking in males whereas in females TP segment indicated significant difference in all three conditions. There was a significant increase in T wave time in males during talking in comparison with resting and ringing; however there was no significant difference in that of females in any of the three stated conditions. This study revealed that there is not any significant difference in PR interval, Time of QRS wave and R wave voltage. CONCLUSIONS: According to the results of this study, mobile phones can affect the heart rate, TP segment and time of T wave. Therefore, it seems that long term use can affect heart. Based on several reports on the effects of these waves on biological processes, precautionary measures should be taken about using mobile phones.