Anticonvulsant and ameliorative effects of pioglitazone on cognitive deficits, inflammation and apoptosis in the hippocampus of rat pups exposed to febrile seizure

Objective(s): Pioglitazone (PGZ), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, has significant neuroprotective effects and has been reported to regulate inflammatory processes.Materials and Methods: We evaluated the effects of PGZ on febrile seizure (FS) in rat pups. Three groups of male rat pups received intraperitoneal (IP) injections of PGZ (5, 10, and 20 mg/kg). Lipopolysaccharide (LPS) and kainic acid (KA) were injected to induce FS. The rat pups behaviors were recorded and analyzed. Seizure latency, duration, and severity were recorded to evaluate the effect of PGZ on FS. Novel object recognition task (NORT) was used to evaluate the effect of PGZ on cognitive deficits induced by FS. At the end of the experimental protocol, molecular and histological tests were done.Results: PGZ significantly increased seizure latency and decreased seizure duration and median of seizure scores (

Effects of multiple doses of montmorillonite, alone and in combination with activated charcoal, on the toxicokinetics of a single dose of digoxin in rats

Objective(s): A narrow margin between the therapeutic and toxic doses of digoxin can result in an increased incidence of toxicity.  Since digoxin has an enterohepatic cycle, multiple oral doses of absorbents like montmorillonite may be useful in the treatment of digoxin toxicity.Materials and Methods: In this study, 4 groups of 6 rats received intraperitoneal digoxin (1 mg/kg), and half an hour later, distilled water (DW) or oral adsorbents, including montmorillonite (1 g/kg), activated charcoal (1 g/kg) (AC) alone or in combination in the ratio of 70:30. Half of the mentioned doses were also gavaged at 3 and 5.5 hr after digoxin injection. The serum level of digoxin, biochemical factors, and activity score were assessed during the experiment. Three control groups only received DW, montmorillonite, or AC.Results: All adsorbents were able to significantly decrease the serum level of digoxin compared to the digoxin+DW group (P<0.01). Only montmorillonite reversed the digoxin-induced hyperkalemia (P<0.05). Multiple dose administration of adsorbents also significantly reduced the digoxin area under the curve and half-life and increased digoxin clearance (P<0.05). However, there was no significant difference in the kinetic parameters between groups that received digoxin plus adsorbents.Conclusion: Multiple-dose of montmorillonite reversed digoxin toxicity and reduced serum digoxin levels by increasing the excretion and reducing the half-life. Montmorillonite has also corrected digoxin-induced hyperkalemia.  Based on the findings, a multiple-dose regimen of oral montmorillonite could be a suitable candidate for reducing the toxicity issue associated with drugs like digoxin that undergo some degree of enterohepatic circulation

TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats

Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke

Commentary: Comment on the Effect of Endocannabinoid System on Rat Behavior

I read the recently published article in Vol 6 (3) of Basic and Clinical Neuroscience entitled &ldquo;Study the Effect of Endocannabinoid System on Rat Behavior in Elevated Plus- Maze&rdquo; by Komaki et al. (2015). In this valuable article, the authors uncovered the effects of AM251 as a CB1 receptor antagonist on anxiety-like behaviors of rats using elevated plus-maz

The effect of intracerebroventricular administration of orexin receptor type 2 antagonist on pentylenetetrazol-induced kindled seizures and anxiety in rats

Abstract Background Current antiepileptic drugs are not able to prevent recurrent seizures in all patients. Orexins are excitatory hypothalamic neuropeptides that their receptors (Orx1R and Orx2R) are found almost in all major regions of the brain. Pentylenetetrazol (PTZ)-induced kindling is a known experimental model for epileptic seizures. The purpose of this study was to evaluate the effect of Orx2 receptor antagonist (TCS OX2 29) on seizures and anxiety of PTZ-kindled rats. Results Our results revealed that similar to valproate, administration of 7 µg/rat of TCS OX2 29 increased the latency period and decreased the duration time of 3rd and 4th stages of epileptiform seizures. Besides, it significantly decreased mean of seizure scores. However, TCS OX2 29 did not modulate anxiety induced by repeated PTZ administration. Conclusion This study showed that blockade of Orx2 receptor reduced seizure-related behaviors without any significant effect on PTZ-induced anxiety

Achillea millefolium Aqueous Extract does not Impair Recognition Memory in Mice

Purpose: To investigate the effect of the aqueous extract of Achillea millefolium on recognition memory in mice. Methods: Male mice (35) were used. The aqueous extract of A. millefolium was prepared using a Soxhlet apparatus and injected intraperitoneally in a dose of 50, 250, 500 or 1000 mg/kg daily for 20 days. The control group was treated with saline 1 ml/mouse/day. Tactile learning was assessed using the novel object recognition test (NORT) in a dark room which entailed measurement of the distance travelled during trial and test phases. Results: Treatment with different doses of A. millefolium did not affect activity levels (based on the distance travelled during trial and test phases). The total time and frequency of visits to the sample objects in trial and test phases were not statistically significant between control and A. millefolium treated groups (p > 0.05). A comparison of the discrimination ratio between the experimental groups revealed no difference. Administration of A. millefolium extract for 20 days did not decrease body weight or cause death in the treated animals. Conclusion: The result of this study demonstrates that chronic treatment with different doses of the aqueous extract of A. millefolium did not impair recognition memory in mice

Drug Abuse among University Students of Rafsanjan, Iran

Objective: The present study aimed to determine the frequency of drug abused in a sample of university students in Rafsanjan, Iran. Methods: In this cross-sectional study, 1,260 students volunteered (311 males and 949 females) with mean age of 21.35 years. Data were collected by a self-administrated questionnaire regarding drugs abuse and demographic information. Results: Benzodiazepines were the most common abused drugs which were reported in 94 students (7.4%). Other agents studied were cigarette and tobacco (159, cases 12.6%), alcoholic drinks (60 cases, 4.7%), and opiates (42 cases, 3.3%). Forty-three students (3.4%) had used methylphenidate in the last 6 months. Of this, 39 (90.6%) experienced insomnia. All students who abused methylphenidate indicated that the reason for this behavior was to raise alertness and conscious levels. Conclusion: The pattern of drug abuse among the students here seems similar to other reports from Iranian universities