Application of vasoactive and matrix-modifying drugs can improve polyplex delivery to tumors upon intravenous administration.

Low efficacy of cationic polymer-based formulations (polyplexes) for systemic gene delivery to tumors remains the crucial concern for their clinical translation. Here we show that modulating the physiological state of a tumor using clinically approved pharmaceuticals can improve delivery of intravenously injected polyplexes to murine melanoma tumors with different characteristics. Direct comparison of drugs with different mechanisms of action has shown that application of nitroglycerin or losartan improved extravasation and tumor uptake of polyplex nanoparticles, whereas angiotensin II had almost no effect on polyplex accumulation and microdistribution in the tumor tissue.

Dynamics of the Development of Amnesia Caused by Disruption of Memory Reconsolidation by Neurotransmitter Receptors Antagonists.

The dynamics of amnesia development under conditions of memory reconsolidation disruption by serotonin receptor antagonist methiothepin or NMDA glutamate receptor antagonist MK-801 was studied in snails trained in conventional food aversion. In 2 days after training, injection of methiothepin or MK-801 before reminder induced amnesia development. During repeated training in 3 days after amnesia induction, the skill was formed more rapidly than during the initial training.

The misfolded pro-inflammatory protein S100A9 disrupts memory via neurochemical remodelling instigating an Alzheimer's disease-like cognitive deficit.

Memory deficits may develop from a variety of neuropathologies including Alzheimer's disease dementia. During neurodegenerative conditions there are contributory factors such as neuroinflammation and amyloidogenesis involved in memory impairment. In the present study, dual properties of S100A9 protein as a pro-inflammatory and amyloidogenic agent were explored in the passive avoidance memory task along with neurochemical assays in the prefrontal cortex and hippocampus of aged mice.

A Hardware-and-Software System for Experimental Studies of the Acoustic Startle Response in Laboratory Rodents.

We developed and tested a novel hardware-and-software system for recording the amplitude of the acoustic startle response in rodents. In our experiments, the baseline indexes of acoustic startle response in laboratory rats and pre-stimulation inhibition under the standard delivery of acoustic stimulation were similar to those evaluated by other investigators on foreign devices. The proposed system is relatively cheap and provides the possibility of performing experiments on freely moving specimens.

Transcription inhibitors prevent amnesia induced by NMDA antagonist-mediated impairment of memory reconsolidation.

Recent studies report that long-term memory retrieval can induce memory reconsolidation, and impairment of this reconsolidation might lead to amnesia. Previously, we found that reconsolidation of a conditioned food aversion memory could be disrupted by translation inhibitors for up to 3 h following a reconsolidation event, thus inducing amnesia. We examined the role of transcription processes in the induction of amnesia in the land snail, Helix lucorum.

Behavioral Indexes of Thermal Nociceptive Sensitivity in Rats after Melatonin Administration.

We studied the effect of melatonin (10 mg/kg intraperitoneally) on behavioral indexes reflecting changes in nociceptive sensitivity of rats in response to thermal stimulation in the hot plate test. Administration of melatonin to animals suppressed the perceptual component of nociception, which was manifested in an increase in the perception threshold of noxious thermal stimulus. In the follow-up period, exogenous melatonin contributed to a decrease in the latency of avoidance reactions and enhanced the behavior of escaping the thermal nociceptive stimulation.

State of Stress-Marker Organs in Rats with Various Behavioral Characteristics during Repeated Stress Exposures.

Changes in the relative weight of stress-marker organs in rats with various behavioral patterns in the open-field test were studied after repeated stress exposures on the model of daily 4-h immobilization over 8 days. Involution of the thymus and spleen in behaviorally passive specimens was found after single stress, as well as under conditions of 3- and 8-fold immobilizations. The weight of these organs in active animals remained practically unchanged after acute stress, but decreased on day 3 and particularly on day 8 of repeated stress exposures.

Reconsolidation of Reminder-Induced Amnesia: Role of NMDA and AMPA Glutamate Receptors.

We studied the role of glutamate receptors and reminder in the mechanisms of amnesia maintenance caused by disruption of conditioned food aversion reconsolidation with an antagonist of NMDA glutamate receptor in snails. At the early stage of amnesia (day 3 after induction), injection or NMDA of AMPA glutamate receptor antagonists prior to reminder (presentation of the conditioned food stimulus) led to memory recovery. Reminder alone or injection of antagonists without reminder or after reminder was ineffective.

Nociceptive Reactions in Rats during Repeated Stress Exposure.

Changes in nociceptive sensitivity of rats with various behavioral patterns in the open-field test were studied after repeated stress exposure on the model of daily 4-h immobilization for 8 days. The tail-flick latency in response to light-heat stimulation in passive and active specimens decreased most significantly on days 2 and 7, respectively. However, this parameter did not differ from the baseline on day 8 of observations.

Effect of NMDA, a Specific Agonist to NMDA Receptor Complex, on Rat Hippocampus.

Removal of Mg2+ ions from perfusion medium provoked epileptiform activity in CA1 field of surviving rat hippocampal slices manifested in generation of extra population spikes. MK-801 (100 μM), a specific non-competitive antagonist to NMDA-receptor complex, prevented this effect. NMDA (20 μM), the specific agonist to this complex, produced no significant effect on the orthodromic population spikes, but when applied at concentrations of 30 or 40 μM, it inhibited them partially (by 21-28%) or almost completely (by 98-99%), correspondingly.

Behavioral and Hemodynamic Effects of Free and Protein-Bound Angiotensin IV in Rats in Experimental Hypo- and Hyperglycemia: Comparative Aspects.

In rats with acute hypo- and hyperglycemia the initial effects of free angiotensin IV and its complexes with functionally different carrier proteins (transport protein BSA, neuron-specific protein S100b) on hemodynamics and behavior of rats were qualitatively altered, in comparison with those in intact animals. At the same time, free angiotensin IV under conditions of hypo- and hyperglycemia paradoxically acquired functions of angiotensin II (moderate hypertension, tachycardia, polydipsia and activation of instrumental drinking behavior). Concurrently, complexes of angiotensin IV with BSA and S100b acquired functions of free angiotensin IV (hypotensia, suppression of drinking behavior).

Spatial Organization of Alpha Range Potentials on EEG and Logical Thinking Effectiveness.

We studied spatial organization of EEG alpha range potentials in volunteers with different results of tasks requiring logical thinking. The examinees with higher cognitive test performance have more labile coherent associations of EEG alpha range potentials, which manifested in changes in the level and structure of these associations at different stages of the test. In individuals with poor results, the number of significant coherent associations and their structure do not change during the problem solving process.

Involvement of Mζ-Like Protein Kinase in the Mechanisms of Conditioned Food Aversion Memory Reconsolidation in the Helix lucorum.

We studied the involvement of Mζ-like protein kinase (PKMζ) into mechanisms of conditioned food aversion memory reconsolidation in Helix lucorum. Injections PKMζ inhibitor ZIP in a dose of 5 mg/kg on day 2 or 10 after learning led to memory impairment and amnesia development. Injections of the inhibitor in doses of 1.

Frequency and Spatial and Temporal Characteristics of Neuronal Spike Activity in Dorsal Hippocampal Field CA1 in Behaviorally Active and Passive Rats after Stimulation of the Lateral and Ventromedial Hypothalamus.

We studied the neuronal mechanisms of the various emotional and motivational states in Wistar rats with different behavioral activities. Stimulation of the ventromedial hypothalamus had more pronounced effect on the frequency of action potentials in neurons of the dorsal hippocampus than stimulation of the lateral hypothalamus. However, stimulation of the lateral hypothalamus produced stronger effect on spatial and temporal characteristics of fi ring pattern than stimulation of the ventromedial hypothalamus.

Antagonists of Metabotropic Glutamate Receptors Prevent the Development of Audiogenic Seizures.

Pretreatment with mGluR1 antagonist AIDA (1 mg/kg) nearly completely prevented the onset of tonic-clonic seizures and increased generation of NO in the cerebral cortex of rats with genetically determined audiogenic reaction to acoustic stimulation. Administration of mGluR5 antagonist MPEP (10 mg/kg) before audiogenic exposure was followed by a significant decrease in the degree of seizure and partially prevented increased generation of NO due to acoustic stimulation. These data indicate that mGlu receptors and NO play an important role in the pathogenetic mechanisms of audiogenic seizures.

Effect of interleukin-4 on peripheral blood leukocytes in rats with various behavioral characteristics during acute stress.

We studied the effect of anti-inflammatory cytokine IL-4 (5 μg/kg intraperitoneally) on peripheral blood leukocytes in Wistar rats with various behavioral characteristics during acute emotional stress (1-h immobilization with simultaneous subthreshold electrocutaneous stimulation). IL-4 reduced the differences in blood leukocyte count in rats with various behavioral characteristics, which was related to a significant decrease in this parameter in active animals. IL-4 injection to active animals was accompanied by changes in the leukogram (development of neutrophilia, monocytopenia, and lymphopenia) and had a modulatory effect on leukocyte indexes of cell reactivity.

Involvement of protein kinase Mζ in the maintenance of long-term memory for taste aversion learning in young chicks.

The effects of an inhibitor of protein kinase Mζ on long-term memory were studied using the model of taste aversion in newborn chicks. Memory was impaired by intracerebral injection of 10 or 20 nmol of ζ-inhibiting peptide 24 h after training. Memory impairment was found 2 h after peptide administration, and repeated examination 24 h after treatment showed no recovery.

Effect of peptide agonists of peripheral opioid receptors on operant feeding behavior and food motivation in rats.

We studied the effect of intragastric administration of peptide agonists of μ-opioid receptors (DAMGO) and δ-opioid receptors (DADLE) on food consumption and food motivation during operant feeding behavior of different intensity and effectiveness. To obtain one food granule, trained rats should press a lever 1 time (day 1), 2 times (day 2), 4 times (day 3), 8 times (day 4), 16 times (day 5), or 32 times (day 6). Activation of δ-opioid receptors in the stomach was followed by suppression of feeding behavior at low energy expenditure.

Learning ability is a key outcome determinant of GSK-3 inhibition on visuospatial memory in rats.

Learning aptitude has never been a focus of visuospatial performance studies, particularly on memory consolidation and reconsolidation. The aim of this study was to determine the consequences of learning ability on memory consolidation/reconsolidation following inhibition of glucose synthase kinase-3 (GSK-3) by 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8). The anxiety-like nature of rats was characterized in the elevated plus maze.

Method for determining the level of food motivation in rats.

A new method for the quantitative evaluation of the level of food motivation was developed. This method takes into account not only the information, but also the energy component of operant feeding behavior of different intensity and effectiveness with a simultaneous study of metabolism by means of indirect calorimetry. Our experiments showed that an increase in the number of lever pressing episodes (from 1 to 8) to obtain one food granule during operant feeding behavior is accompanied by a progressive decrease in the level of food motivation.

Peripheral administration of a μ-opioid receptor agonist DAMGO suppresses the anxiolytic and stimulatory effects of caffeine.

We studied the possibility of modulation of the stimulatory and anxiolytic effects of caffeine by activation of μ-opioid receptors in the gastrointestinal tract. Caffeine in a dose of 10 mg/kg (but not in a dose of 100 mg/kg) had a strong anxiolytic and psychostimulant effect. This effect was manifested in a significant increase in the time spent in the open arms of the elevated plus-maze, elevation of locomotor activity, and stimulation of metabolism.

Study of behavioral parameters during learning of rats in an operant feeding task and evaluation of biochemical indexes after dietary consumption of the phytoecdysteroid extract.

Experiments on rats were performed to study the process of operant feeding learning, locomotor activity, oxygen consumption, and concentrations of corticosterone, β-endorphin, and prostaglandin E in blood serum after dietary treatment with the phytoecdysteroid extract. Administration of phytoecdysteroids was followed by the improvement of learning and increase in oxygen consumption and locomotor activity. Locomotor activity and oxygen consumption in the majority of control rats and phytoecdysteroid-treated animals were shown to be interrelated with the total locomotor activity and goal-directed operant behavior, respectively.

Correlation dependencies between nociceptive sensitivity and cytokine level in biological fluids of rats after administration of lipopolysaccharide.

Correlation dependencies between nociceptive sensitivity and cytokine level in biological tissues of rats were studied on days 1 and 7 after antigenic stimulation due to intraperitoneal injection of LPS (30 μg/kg). No correlations were found between the nociceptive thresholds and cytokine contents in the dorsal hippocampus and anterior cingulate cortex of animals. Inverse correlations between the tail-flick latency in response to nociceptive stimulation and concentrations of an anti-inflammatory cytokine IL-10 and pro-inflammatory cytokine TNF-α in the peripheral blood of rats were revealed on day 7 after LPS injection.

Long-term phase reorganization of conditioned food aversion memory in edible snail.

The specific features of memory reconsolidation in edible snails were studied over 30 days after learning of conditioned food aversion. Injections of a NMDA glutamate receptor antagonist MK-801 or protein synthesis inhibitor cycloheximide in combination with the conditioned food stimulus (reminder) on day 2 after learning were followed by the development of amnesia. Repeated training on day 10 after the induction of amnesia did not result in skill formation.