Cannabinoid receptor agonism suppresses tremor, cognition disturbances and anxiety-like behaviors in a rat model of essential tremor

Cognitive and motor disturbances are serious consequences of tremor induced by motor disorders. Despite a lack of effective clinical treatment, some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of tremor. In the current study, the effects of WIN55, 212-2 (WIN), a cannabinoid receptor (CBR) agonist, on harmaline-induced motor and cognitive impairments were studied. Adult rats were treated with WIN (0.5 mg/kg; i.p.) 15 min before harmaline administration (10 mg/kg; ip) after which exploratory and anxiety related behaviors, and cognitive function were assessed using open-field behavior and shuttle box tests. Rats that received harmaline only exhibited a markedly reduced number of central square entries when compared to harmaline vehicle-treated controls, whereas those treated with WIN and harmaline showed a significant increase in central square entries, compared to harmaline only treated. The passive avoidance memory impairments observed in harmaline treated rats, was reversed somewhat by administration of WIN. The neuroprotective and anxiolytic effects of WIN demonstrated in the current study can be offered cannabinoid receptor (CBR) agonism as a potential neuroprotective agent in the treatment of patients with tremor that manifest mental dysfunctions

Oil-In-Water Microemulsion Encapsulation of Antagonist Drugs Prevents Renal Ischemia-Reperfusion Injury in Rats

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received “conventional” SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the future

The effect of long term administration of ascorbic acid on the learning and memory deficits induced by diabetes in rat

"n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Ascorbic acid improves cognitive impairments in several experimental models. Diabetes causes learning and memory deficits. In this study we hypothesized that chronic treatment with ascorbic acid (100mg/kg, p.o) would affect on the passive avoidance learning (PAL) and memory in control and streptozocin-induced diabetic rats."n"nMethods: Diabetes was induced by a single i.p. injection of STZ (60mg/kg). The rats were considered diabetic if plasma glucose levels exceeded 250mg/dl on three days after STZ injection. Treatment was begun at the onset of hyperglycemia. PAL was assessed 30 days later. Retention test was done 24 h after training. At the end, animals were weighted and blood samples were drawn for plasma glucose measurement."n"nResults: Diabetes caused impairment in acquisition and retrieval processes of PAL and memory in rats. Ascorbic acid treatment improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. Ascorbic acid administration also improved the body weight loss and hyperglycemia of diabetics. Hypoglycemic and antioxidant properties of the vitamin may be involved in the memory improving effects of such treatment."n"nConclusion: These results show that ascorbic acid administration to rats for 30 days from onset of diabetes alleviated the negative influence of diabetes on learning and memory. Comparing with other nootropic drugs, vitamins have fewer side effects. Therefore, this regimen may provide a new potential alternative for prevention of the impaired cognitive functions associated with diabetes after confirming by clinical trials

Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats

Context: Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects. Objective: The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated. Materials and methods: Male Wistar rats were pretreated with RA (10, 50 and 100 mg/kg, i.g.) for one week. On day 7, rats received APAP (500 mg/kg, i.p.). Then aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein, malondialdehyde (MDA), glutathione (GSH), total antioxidant capacity (TAC), glutathione S-transferase (GST), cytochrome CYP450 and histopathological changes were determined. Results: APAP-induced oxidative stress in liver by a significant increase in the level of MDA (7.6 ± 0.21 nmol/mg) as well as a decrease in the contents of TAC (1.75 ± 0.14 μmol/g), GSH (1.9 ± 0.22 μmol/g) and GST) 3.2 ± 0.28 U/mg). RA treatment decreased MDA (4.32 ± 0.35 nmol/mg) but increased the contents of TAC (3.51 ± 0.34 μmol/g), GSH (3.42 ± 0.16 μmol/g) and GST (5.71 ± 0.71 μmol/g) in APAP group. RA 100 mg/kg decreased ALT (91.5 ± 1.5 U/L), AST (169 ± 8.8 U/L) and CYP450 (3 ± 0.2 nmol/min/mg) in APAP group. Histologically RA attenuated hepatic damage by decreasing necrosis, inflammation, and haemorrhage in liver sections of APAP group. Discussion and conclusions: This is the first report that oral administration of RA dose-dependently elicited significant hepatoprotective effects in rats through inhibition of hepatic CYP2E1 activity and lipid peroxidation. RA-protected hepatic GSH and GST reserves and total tissue antioxidant capacity

Oil-In-Water Microemulsion Encapsulation of Antagonist Drugs Prevents Renal Ischemia-Reperfusion Injury in Rats

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received “conventional” SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the future

Comparing the Antinociceptive Effects of Methamphetamine, Buprenorphine, or Both After Chronic Treatment and Withdrawal in Male Rats

Introduction: Methamphetamine (Meth) and Buprenorphine (BUP) modulate pain perception. However, the antinociceptive effects of their interactions, which affect through different systems, are unclear in rats. This study aimed to compare the analgesic effects of Meth, BUP, and their coadministration, as well as the effect of withdrawal from these substances on nociception in male rats. Methods: In this experiment, 40 male Wistar rats (weight: 250-300 g) were categorized into four groups: control, Meth, BUP, or BUP+Meth. After seven days of treatments, the antinociceptive effects were assessed using the hot plate and the tail flick tests. The differences among the groups were analyzed with ANOVA and Tukey’s post hoc tests. P values less than 0.05 were considered significant. Results: Meth and BUP increased the reaction times during the hot plate and tail flick tests. The combination of Meth and BUP increased reaction time more than Meth or BUP alone.  Conclusion: The significantly high reaction times in rats treated with Meth and BUP indicate that these substances have antinociceptive effects. In addition, Meth enhanced the antinociceptive effects of BUP. These synergistic effects might occur through the dopaminergic, serotonergic, and or adrenergic systems

Effects of Neonatal C-Fiber Depletion on Interaction between Neocortical Short-Term and Long-Term Plasticity

Introduction: The primary somatosensory cortex has an important role in nociceptive sensory-discriminative processing. Altered peripheral inputs produced by deafferentation or by long-term changes in levels of afferent stimulation can result in plasticity of cortex. Capsaicin-induced depletion of C-fiber afferents results in plasticity of the somatosensory system. Plasticity includes short-term and long-term changes in synaptic strength. We studied the interaction between paired-pulse facilitation, as one form of short-term plasticity, with long-term potentiation (LTP) in the neocortex of normal and C-fiber depleted freely moving rat. Methods: Neonatally capsaicin-treated rats and their controls were allowed to mature until they reached a weight between 250 and 300g. Then animals were anesthetized with ketamine and xylazine. For recording and stimulation, twisted teflon-coated stainless steel wires were implanted into somatosensory cortex or corpus callusom. In experiments for LTP induction, after two weeks of recovery period, 30 high frequency pulse trains were delivered once per day for 12 days. Paired-pulse ratio (PPR) was monitored before and after the induction of LTP in capsaicin-treated and control rats. Results: Paired-pulse stimulation affected all field potential components at intervals < 200 ms. The largest changes occurred at intervals between 20- 30 ms. C-fiber depletion postponed the development of LTP, whereas it had no effect on PPR. Discussion: This finding provides further evidence that the expression of this form of LTP is postsynaptic. Furthermore, these results suggest that the effect of C-fiber depletion on cortical LTP is also postsynaptic and, therefore, is not caused by a decrease in neurotransmitter release

The Role of Parabrachial GABAA Receptors in Pain Modulation in Rats

Background & Objective: The parabrachial nucleus is a critical link in the transmission of short latency nociceptive information to midbrain neurons. GABA(A) receptors have bidirectional roles in controlling nociception and are abundant in the parabrachial region . We examined the effects of bilateral intra parabrachial microinjection of different doses of the GABA(A) receptor agonist, muscimol, and the GABA(A) receptor antagonist, bicuculline, on pain modulation using a tail-flick test . Materials & Methods: Rats were anaesthetized with sodium pentobarbital (55 mg/kg) and then special cannulas were inserted stereotaxically into the parabrachial nucleus. After 1 week of recovery, the effects of microinjection of muscimol, (62.5, 125,250 ng/side) or bicuculline, (50,100,200 ng/side) into the parabrachial on tail flick latencies were assessed. Tail-flick latencies were measured for 60 minutes every 5 min after drug microinjection. Results: Microinjection of muscimol (62.5, 125 ng/side) and bicuculline (50,100,200 ng/side) into the parabrachial did not have any statistically significant effect on tail-flick latency. Administration of, muscimol, (250 ng/side) produced thermal hyperalgesia (P<0.05). Conclusion: The results of the present study showed that in this model of pain gaba a receptors in the paracrachial region are not Endogenously activated but these receptors in this region have a potential to affect pain modulation