Memory Effects of Benzodiazepines: Memory Stages and Types Versus Binding-Site Subtypes

Benzodiazepines are well established as inhibitory modulators of memory processing. This effect is especially prominent when applied before the acquisition phase of a memory task. This minireview concentrates on the putative subtype selectivity of the acquisition-impairing action of benzodiazepines. Namely, recent genetic studies and standard behavioral tests employing subtype-selective ligands pointed to the predominant involvement of two subtypes of benzodiazepine binding sites in memory modulation. Explicit memory learning seems to be affected through the GABAA receptors containing the α1 and α1 subunits, whereas the effects on procedural memory can be mainly mediated by the α1 subunit. The pervading involvement of the α1 subunit in memory modulation is not at all unexpected because this subunit is the major subtype, present in 60% of all GABAA receptors. On the other hand, the role of α5 subunits, mainly expressed in the hippocampus, in modulating distinct forms of memory gives promise of selective pharmacological coping with certain memory deficit states

Adjunctive effect of the colloidal silver ions solution in the treatment of chronic periodontal disease: A preliminary clinical study

Background/Aim. Bacteria play the most important role in the development of periodontitis and chlorhexidine (CHX) is a “gold standard” in its treatment. Silver ions are also strong antiseptics, being used in dentistry for a long time. Therefore, the aim of this study was to compare the efficacy of CHX and colloidal silver ions solution (SSI) in the treatment of patients with chronic periodontitis. The additional aim was to ascertain silver ions, tolerability and efficacy comparing to CHX. Methods. Twenty-nine examinees of both sexes (the average age 50.6) participated in this study and were divided into two groups. The patients in the first group (n = 15) suffering from a generalized moderate chronic periodontitis, after scaling and root planning (SRP), were treated by rinsing of periodontal pockets with 0.2% solution of CHX. The patients of the second group (n = 14), in addition to the treatment of periodontal pockets, were treated with a 5 mg/mL colloidal SSI. Results. During the periodontal treatment, the mean values of all clinical parameters (except clinical attachment loss – CAL), in the both groups of patients were statistically significantly lower (p < 0.001) in relation to the initial values. The greater reduction of periodontal bleeching on probing (BOP) depth after one month was found in the SSI treated group (0.97 mm) in relation to the CHX group (0.65 mm). The local application of CHX and SSI led to statistically significant reduction of gingival parameters (gingival index – GI and BOP) in the groups after the treatment (GI for 0.65 and 0.87; BOP for 0.31 and 0.33, respectively). Conclusion. The results of our study showed that colloidal SSI was at least equally effective in the treatment of patients with periodontal disease as the solution of CHX. Additionally, the SSI is simple for use which speaks in favor of its more extensive use in dentistry including chronic periodontal disease

Beneficial Effects of Ceftriaxone Against Pentylenetetrazole-Evoked Convulsions

Although considered to be generally safe, a number of P-lactam antibiotics have been associated with epileptic seizures in humans. Furthermore, some P-lactam antibiotics, including ceftriaxone, are used to evoke convulsions under experimental conditions. Recently it was demonstrated that ceftriaxone increased expression of the glutamate transporter (GLT1) and its biochemical and functional activity in the brain of rodents. GLT1 regulates extracellular concentrations of glutamate, an excitatory amino acid involved in the pathogenesis of seizures and epilepsy. Because of its rapid transfer of glutamate into neurons and adjacent glial cells, GLT1 diminishes glutamate toxicity. We investigated whether ceftriaxone (200 mg/kg body wt) administered intraperitoneally (ip) for 6 days could modify the convulsant effects of pentylenetetrazole (PTZ, 100 mg/kg ip) in inbred male BALBcAnNCR and C57 black (BL)/6 mice aged 4 and 12 weeks. Ceftriaxone pretreatment provided significant protective effects against PTZ-evoked generalized clonic convulsions (GCCs), generalized clonic-tonic convulsions (GCTCs), and convulsion-induced mortality during a period of 30 mins after PTZ administration. The incidence of GCCs, GCTCs, and death was statistically significantly lower for BALBcAnNCR mice of both ages, particularly younger mice. The latency time for each of the three parameters was significantly greater, with the exception of GCCs in adult mice. Protective effects of ceftriaxone were also noticed in adult C57BL/6 mice but not in prepubertal C57BL/6 mice. This is the first demonstration of anticonvulsant effects of ceftriaxone or any other P-lactam antibiotic, which are not uniform across the mouse population. Our results provide new insight into the effects of ceftriaxone, which need further investigation. Exp Biol Med 233:1389-1394, 2008Ministry or Science of the Republic of Serbia [143057

Influence of Midazolam and L-Arginine on Clinical Observations and Biochemical Changes in Rat Liver Induced by Pentylenetetrazole

Certain types of convulsions may lead to multiorgan dysfunction. We investigated whether the chemoconvulsant pentylenetetrazole (PTZ) could influence energy synthesis in the liver besides evoking convulsions in adult male Wistar rats. In 80% of the rats PTZ (100 mg/kg body weight, administered intraperitoneally - i.p.) evoked generalised clonic convulsions (GCCs) and in 60% of the rats generalised clonic-tonic convulsions (GCTCs) within 4 min after its administration. Cytochrome c oxidase activity was simultaneously reduced approximately three-fold compared to 0.9% NaCl-treated (control) rats (p < 0.01). Midazolam administered before PTZ was an excellent anti-convulsant especially against GCCs (p < 0.05). However, it did not protect against the decrease in cytochrome c oxidase activity induced by PTZ. In contrast to midazolam, pretreatment with L-arginine did not prevent PTZ-evoked convulsions. However, it offered some protection against the PTZ-mediated reduction in cytochrome c oxidase activity. Our results open new avenues of research that will focus on the mechanisms of action of PTZ, midazolam and L-arginine with particular reference to their direct and/or indirect effects on liver function.Ministry of Science of the Republic of Serbia [143057

Basic mechanisms of the cellular alterations in T-2 toxin poisoning: Influence on the choice and result of the therapy

T-2 mycotoxin, secondary metabolite of Fusarium fungi, is one of the most potent cytotoxic representatives of trichothecene mycotoxin type A. After ingestion, T-2 toxin affects actively dividing cells and irreversible post-mitotic cells. In our experiments, the best protective effects were produced by dexametasone (PI = 3.37) and different methylprednisolone formulations (PI = 2.43-2.64). Significant protective efficacy was shown by nimesulide (PI = 1.44) and N-acethyilcistein (PI = 1.29), but their values were higher in a combination with methylprednisolone (PI = 2.16-2.34). Radioprotector amifostine (WR-2721) expressed good protective effects (PI = 1.26) or/and different absorbent formulations, such as: activated charcoal (PI = 1.13) and various Min-a-zel® powder compounds, which are a well known zeolite clinoptilolite absorbents. Among the five zeolite regimens investigated, only Min-a-zel Plus® showed a significant protective effect (PI = 1.77). In summary, the steroidal anti-inflammatory drugs could be recommended as a regimen of choice for treatment of acute T-2 toxicosis while nonsteroidal anti-inflammatory compounds, different absorbent formulations and their combinations with antioxidants or radioprotectors could be important for the treatment of subacute and chronic T-2 toxin poisonings

Learning and memory in nucleus basalis magnocellularis-lesioned rats after transplantation of fetal frontal cortex

The effect of fetal frontal cortex transplantation on behaviour performance was examined in adult male Wistar rats with lesions of the nucleus basalis magnocellularis (NBM). Compared to intact and sham-operated controls, the rats tested ten or twenty days after bilateral electrolytic lesions of NBM exhibited the significant learning and memory impairments (acquisition and performance of two-way active avoidance) whereas spontaneous motor activity was not significantly altered. The animals which received allotransplants of fetal frontal cortex (from 18-day gestational rat fetuses) into NBM, two (''early'' transplantation -NBM-ET) or ten (''delayed'' transplantation-NBM-DT) days after lesioning, respectively, manifested the complete amelioration of noticed impairments when tested ten days after transplantation procedure. Corresponding sham-transplants groups (NBM-SET and NBM-SDT) showed only slightly improvement of acquisition but not performance of two-way active avoidance. The ability of the transplants to restore learning and memory in the NBM lesioned rats suggests that graft of fetal frontal cortex can functionally influence neuronal activity of the lesioned host brain

Effect of physostigmine and verapamil on active avoidance in an experimental model of Alzheimer's disease

The present study was performed to investigate and compare the effect of acetylcholinesterase inhibitor, physostigmine (0.045, 0.060 and 0.075 mg/kg sc, 30 min before the tests) and Ca-antagonist, verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg sc, 30 min before the tests), on two-way active avoidance (AA) learning (acquisition and performance) in nucleus basalis magnocellularis (NBM)-lesioned rats. Bilateral electrolytic lesions of NBM induced significant decrease of acquisition and performance of AA responses in rats. Physostigmine (0.060 mg/kg) significantly improved only acquisition of AA, while verapamil (2.5 and 5.0 mg/kg) significantly improved both type of AA behavior in NBM-lesioned rats. These results suggest that altered calcium homeostasis might play significant role in pathogenesis of experimental induced Alzheimer's disease (AD) and that administration of calcium antagonist such as verapamil might successfully ameliorate disturbances of learning and memory appeared after lesions of NBM

Behavioral and adaptive status in an experimental model of Alzheimer's disease in rats

Ten days after bilateral electrolytic lesions of nucleus basalis magnocellularis (NBM) we tested behavioral (spontaneous motor activity, acquisition and performance of two-way active avoidance, fear-response in open field test, foot shock induced aggression, depression-response in learned helplessness test) and adaptive status (body temperature at standard, hot and cold environment as well as cold restraint-induced gastric lesions) in adult male Wistar rats. Compared to intact control and sham-operated rats, the bilateral NBM-lesioned rats showed the significant impairment of learning behavior and reduced fear, aggression and depression as well as altered body temperature at standard and stressed conditions. Namely, it was established that body temperature in NBM-lesioned rats was significantly lower at standard laboratory conditions, but in these rats body temperature significantly was raised after exposing to cold and hot environment. On the other hand, spontaneous motor activity and number and length of cold restraint-induced gastric lesions (erosions and petechiae) in NBM-lesioned rats were similarly to those in both controls. It could be concluded that NBM plays a significant role in cognitive, emotional and adaptive processes in the rats