Intraperitoneal injection of buprenorphine on anxiety-like behavior and alteration in expression of Gfap and Nrf2 in methamphetamine treated rats.

The effects of buprenorphine (BUP) on anxiety-like behavior and the expression of the glial fibrillary acidic protein (Gfap) and nuclear factor erythroid 2-related factor 2 (Nrf2) in methamphetamine (METH)-treated rats were investigated in this study. Twenty-eight male Wistar rats were randomly divided into four groups including control (saline), METH (10.00 mg kg-1), BUP (10.00 mg kg-1), and BUP+METH groups and treated for five days. On the final day of treatment, gene expression levels and anxiety were evaluated using elevated plus-maze (EPM). According to the results, five days of METH injection reduced open arm exploration in the EPM. In contrast, the open arm entries and the time spent in the open arms were increased in the BUP+METH group compared to the METH group. The expression levels of Gfap and Nrf2 were lower in METH-treated rats compared to controls, whereas Gfap and Nrf2 expression levels were higher in the METH+BUP-treated rats compared to the METH-treated rats, however, it was similar to the controls. These findings suggested that co-administration of BUP+METH could decrease anxiety-like behavior through increasing the activity of the antioxidant protection system and might have therapeutic potential for preventing anxiety in METH users.

Conjugated Linoleic Acid-Curcumin Attenuates Cognitive Deficits and Oxidative Stress Parameters in the Ethidium Bromide-Induced Model of Demyelination.

Oxidative stress has been shown to play an important role in the pathogenesis of multiple sclerosis (MS). Curcumin (CUR), an antioxidant compound, can be a potent treatment for neurodegenerative diseases, such as MS. CUR has poor bioavailability; therefore, it is used in nanoforms to increase its bioavailability. In the present study, the effects of CUR and conjugated linoleic acid-CUR (Lino-CUR) on spatial memory and oxidative stress in a putative animal model of MS were investigated. Forty-nine adult male Wistar rats (250 ± 50 g) were randomly divided into seven groups (n = 7): control, sham, ethidium bromide (EB), CUR (20 and 40 µg/kg) + EB, and Lino-CUR (20 and 40 µg/kg) + EB groups. Following MS induction, the groups were treated for 5 consecutive days. Finally, spatial memory and levels of oxidative stress parameters were assessed. Treatment with CUR and Lino-CUR at two doses significantly improved spatial memory and reduced oxidative stress parameters in the experimental models of MS. Furthermore, the effects of high dose (40 µg/kg) of Lino-CUR were more remarkable. These findings suggest that the microinjection of CUR in its synthetic form Lino-CUR significantly ameliorated spatial memory, through the reduction of oxidative stress markers in the brain of studied animals as a rat model of MS.

Synergistic effects of quercetin and regular exercise on the recovery of spatial memory and reduction of parameters of oxidative stress in animal model of Alzheimer's disease.

It has widely been reported that the brain in Alzheimer's disease (AD) is affected by increased oxidative stress, and this may have a role in the pathogenesis of this disorder. Quercetin, a polyphenol extensively found in nature, has recently been considered. Also, physical activities have a paradoxical effect on brain function in older adults. Therefore, this study aimed at investigating the synergic effects of quercetin (as chemical treatment) and exercise (as physical treatment) on AD-induced learning and memory impairment. Fifty-six adult male Wistar rats were randomly assigned into one of the following eight groups (n=7): The Control, Sham (saline), AD (intracerebroventricular administration of streptozotocin (STZ)), AD+80 mg/kg Quercetin (STZ+Q80), Quercetin vehicle (1 % Ethanol)+STZ, Exercise pretreatment (EX)+STZ, Off the treadmill+STZ, and EX+Q80+STZ. Quercetin administration was done intraperitoneally for 21 days after STZ injection. The rats ran on the treadmill for one hour a day for 60 days at a speed of 20-22 m/min. After the treatment, the spatial memory and levels of oxidative stress parameters were evaluated. The results showed that STZ caused spatial memory impairment and increased oxidative stress in the hippocampus. Exercise pretreatment or Quercetin injection improved the spatial memory impairment and oxidative stress caused by STZ injection. However, the combination of quercetin and exercise pretreatment was more effective. It can be concluded that the combined exercise pretreatment and Quercetin injection affected the antioxidant defense system and improved STZ-induced memory impairment.

Effects of short- and long-term regular exercise on reproductive tissue in streptozotocin-induced diabetic male Wistar rats.

OBJECTIVE: Reproductive disorders are one of the complications of diabetes mellitus. Since conflicting results have been obtained from different studies, which examined serum levels of cytokines in patients with diabetes, and considering the fact that the origin of cytokines cannot be accurately determined from their serum changes, attempts were made in the present study to study histological changes and testicular tissue levels of TNF-α and IL-1 in rats treated with exercise. Considering the effects of exercise in reducing blood sugar level and its complications, two types of short-term and long-term regular exercises were also considered to evaluate their effects on male reproductive tissues. METHODS: In this study, 60 male rats with the weight range of 250±50 g were used and were randomly divided into six groups (10 rats each). Healthy groups included sedentary control group, and groups treated with two and eight weeks of exercise. Rats with type 1 diabetes (induced by streptozotocin) included sedentary control group, groups treated with two and eight weeks of exercise (six groups). All groups were evaluated in terms of testicular tissue levels of TNF-α and IL-1 using ELISA and the histometry of spermatogonia, primary spermatocytes, Sertoli cells, epithelial thickness, diameter of veins, and thickness of the seminiferous tubule. RESULTS: Histological changes resulting from diabetes, particularly in the diameter of testicular veins and a number of cells, including Sertoli, highlights the important fact that tissue perfusion in patients with diabetes is especially crucial, in a way that exercise proved useful for tissue structures by offsetting this complication. Measurement of the cytokines IL-1 and TNF-α in the current study showed that perfusion problems are more important in diabetic complications than inflammatory factors. CONCLUSIONS: The main result of this research is recommendation of investigating the tissue of interest for diagnosis of diabetes complications, measuring inflammatory mediators of tissue rather than evaluating their serum concentrations, and focusing on vascular complications as a major complication of diabetes. Furthermore, regular exercise could help improve the function of reproductive organs in healthy groups and prevent diabetes infertility complications to an acceptable degree in diabetic groups.

Effect of intrahippocampal administration of vitamin C and progesterone on learning in a model of multiple sclerosis in rats.

PURPOSE: The purpose of this study was to evaluate the effect of intrahippocampal injection of vitamin C and progesterone, alone or in combination, on passive avoidance learning (PAL) in multiple sclerosis. METHODS: Sixty- three male wistar rats were divided into nine groups (n=7) as following: control (saline), lesion, vitamin C (0.2, 1, 5 mg/kg), progesterone (0.01, 0.1, 1 µg/µl) and combination therapy. Lesion was induced by intrahippocampal injection of ethidium bromide. In combination therapy, animals were treated with vitamin C (5 mg/kg) plus progesterone (0.01 mg/kg). Animals in experimental groups received different treatments for 7 days, and then all groups were tested for step through latency (STL). RESULTS: Our results showed that intrahippocampal injection of ethidium bromide destroys PAL significantly (p<0.001). Treatment with vitamin C (5mg/kg) significantly (p<0.05) improved PAL. Lower doses of progesterone did not affect latency but dose of 1 µg/µl significantly (p<0.05) increased STL. In combination therapy group STL was significantly (p<0.05) more than in the lesion group, although it was not significantly different from the vitamin C group. CONCLUSION: Based on our results, we concluded that intrahippocampal injection of vitamin C improves memory for PAL, but progesterone alone or in combination with vitamin C had no improving effects on memory.

Chronic ecstasy use increases neurotrophin-4 gene expression and protein levels in the rat brain.

Ecstasy is a widely abused psychoactive recreational drug that is known to induce neuroplastic effects. The molecular basis of addiction remains poorly understood, but diverse lines of evidence suggest that neurotrophins (BDNF, NT-3 and NT-4) play a role in the regulation of synaptic plasticity. The present study was designed to evaluate the alteration of NT-4 protein levels and gene expression in the brain stem, cerebellum and cerebral hemisphere of rat brains in the context of ecstasy dependence. Ecstasy addiction was induced by intraperitoneal injection of ecstasy (10 mg/kg) for 5 days. After chronic ecstasy treatment, the NT-4 levels in the abovementioned areas of the brain were determined by ELISA. There was a significant increase in the NT-4 protein concentration in the brain stem, cerebellum and cerebral hemisphere when compared with control group. Additionally, these regions were assayed for the transcription of NT-4 using semi-quantitative RT-PCR normalized to ß-actin gene transcription. The results show that chronic administration of ecstasy significantly increased NT-4 gene expression in the abovementioned areas of brain. The current work demonstrates that ecstasy induced-maladaptations may be regulated by NT-4.

Alterations of BDNF and NT-3 genes expression in the nucleus paragigantocellularis during morphine dependency and withdrawal.

Locus coeruleus (LC) plays a key role in opioid dependence and withdrawal. Chronic morphine administration induces neurochemical adaptations in the noradrenergic system. The nature of signal responsible for opiate-induced adaptations of noradrenergic neurons in LC is not well defined. Neurotrophins-signaling pathways such as brain derived neurotrophic factor (BDNF) and Neurotrophin-3 (NT-3) play a key role for regulating the noradrenergic response of LC neurons to opiates. The nucleus paragigantocellularis (PGi) is one of the two major afferents to LC. The present study was designed to evaluate the expression of BDNF and NT-3 in the context of opiate dependence and withdrawal in PGi. Such data are important because they could reveal the role of PGi as an additional source of BDNF and NT-3 in the neurochemical plasticity of LC neurons. Opiate dependence was induced by a progressive intraperitoneal treatment of morphine. In morphine dependent group PGi nucleus was extracted for gene expression assay 6h after the last injection of morphine. In spontaneous withdrawal, rats received the same chronic treatment as morphine group. PGi was extracted for gene expression assay 24, 48 and 72 h after the last injection of morphine. PGi nucleus was assayed for the expression of BDNF and NT-3 using semi-quantitative RT-PCR normalized to beta-actin gene expression. Results showed that chronic administration of morphine significantly increased BDNF and NT-3 gene expression in PGi. In spontaneous withdrawal, BDNF/NT-3 genes expression were high in comparison to control group. It seems that BDNF/NT-3 -signaling pathway originating from PGi is essential for opiate-induced adaptations of the LC neurons.

Additive effect of dextromethorphan on the inhibitory effect of anti-NT4 on morphine tolerance.

It has been proposed that opioid tolerance is a model of neuronal plasticity similar to learning and memory. Recent evidence suggests that neurotrophins may be involved in synaptic development and plasticity. Observations indicate that neurotrophin 4 (NT4) is required for the synaptic plasticity mediating both tolerance and memory. Also there are lines of evidence to indicate that NMDA receptors are involved in the neural plasticity underlying the development of opiate tolerance. Neurotrophins affect central transmission postsynaptically by enhancing NMDA receptor responsiveness. So we used the clinically available NMDA receptor antagonist, dextromethorphan, and the neurotrophin 4 antibody, anti-NT4, concomitantly and alone to investigate their effects on morphine tolerance. Tolerance was induced by injecting morphine (7 and 10 mg/kg i.p.) once per day for 4 days. Anti-NT4 (1 microg/rat i.c.v.) was administered 15 min before morphine. Results showed that chronic concomitant treatment of anti-NT4 with morphine in both doses inhibited the development of morphine tolerance. Also acute treatment of anti-NT4 significantly reversed the tolerance that was induced by morphine 7 mg/kg but failed to reverse the tolerance of morphine 10 mg/kg. Dextromethorphan in both doses (10 or 30 mg/kg) has an additive effect on the inhibitory effect of anti-NT4 on the reversal of morphine tolerance (7 mg/kg). These findings provide additional support for the hypothesis that NMDA receptor and NT4 may be involved in neural plasticity underlying opiate tolerance.