Effect of Nitric Oxide Synthase Inhibitor on the Learning and Spatial Memory in Rats Subjected to Long-Term Perinatal Administration of Caffeine.

We studied the effect of inducible nitric oxide synthase inhibitor aminoguanidine on learning and spatial memory in rats exposed to long-term administration to caffeine during the prenatal and early postnatal periods. The rats perinatally receiving caffeine demonstrated high learning ability in the Morris water maze. At the same time, the ability to remember the location of the hidden platform in the trial probe in these rats was reduced in comparison with that of the control group rats perinatally receiving water. Administration of aminoguanidine to rats under conditions of perinatal exposure to caffeine significantly improved the parameters of spatial learning and memory. Thus, inhibition of inducible nitric oxide synthase has a beneficial effect on the cognitive functions in offspring perinatally receiving caffeine.

The Development of Pathological Dependence after Intermittent Use of Sodium Glutamate, but Not Sucrose or Sodium Chloride Solutions.

The possibility of development of dependence was studied during the intermittent consumption of sucrose, sodium chloride, and sodium glutamate solutions. Rats were allowed to choose and consume solutions of sucrose, sodium chloride, and sodium glutamate for 28 days. On days 29-31 of the experiment, the animals were deprived of the preferred solutions. On days 32-33, the solutions of sucrose, sodium chloride, and sodium glutamate, but not water were provided again. The consumption of sucrose and sodium chloride solutions did not increase, but consumption of 0.5 and 1% sodium glutamate solutions increased after 3-days withdrawal. The consumption of 2% solution of sodium glutamate was the same before and after withdrawal. The observed effects of sodium glutamate deprivation probably indicate the development of pathological glutamate dependence.

Endogenous Opioid Dependence Induced in Rats by Periodic Intake of 5% Ethanol Solution.

We studied the possibility of formation of endogenous opioid dependence in rats during periodic intake of 5% ethanol solution. In the control group, both drinking bottles contained water. In the experimental group, the second bottle was filled with 5% ethanol solution for 12 h per day; in the following 12 h, these rats were deprived of food and ethanol. This regimen was maintained over 8 days. The rats were subdivided into alcohol- and water-preferring subgroups. Ethanol deprivation followed by naloxone injection evoked the signs of opiate withdrawal syndrome in both subgroups. These findings suggest that periodic voluntary intake of a weak ethanol solution over 8 days led to the formation of endogenous opioid dependence in rats irrespective of amount of the consumed alcohol.

Influence of Caffeine Consumption by Pregnant Rats on Behavior and Learning in Their Offspring.

We studied the effect of long-term prenatal administration of caffeine on the behavior and learning of rats in postnatal ontogeny. Experiments were carried out on male rats born by females receiving caffeine solution as the only source of fluid throughout gestation. The control group consisted of pups obtained from females receiving drinking water throughout pregnancy. It was found that long-term caffeine intake by female rats during pregnancy determined increased locomotor activity of the offspring. Rat pups born from mothers treated with caffeine during pregnancy faster reached the underwater platform in the Morris maze, i.e. demonstrated better spatial memory formation than control animals.

Effect of Peripheral µ-, δ-, and κ-Opioid Ligands on the Development of Tolerance to Ethanol-Induced Analgesia.

We studied the rate of development of tolerance to the ethanol-induced analgesia under the effect of µ-, δ-, and κ-opioid agonists and antagonists not crossing the blood-brain barrier and rapidly inactivated by gastric and duodenal proteolytic enzymes. Activation of gastric κ-opioid receptors eliminated the analgesic effect of ethanol and accelerated the development of tolerance to ethanol-induced analgesia. In contrast, activation of gastric µ-opioid receptors decelerated the development of this tolerance. Activation of gastric δ-opioid receptors produced no effect on examined tolerance. µ-Opioid receptor antagonist decelerated and δ-opioid receptor antagonist accelerated the development of tolerance to ethanol-induced analgesia. Thus, the state of gastric opioid receptors affects the manifestation of ethanol-induced analgesia and the development of tolerance to this effect.

New Experimental Model of Rat Risk Behavior. Effects of Nicotine and Phenazepam.

We described a new model of risk behavior in rats that allows selection of animals predisposed to risk behavior in the absence of other biological motivations. Phenazepam administration did not change the intensity of risk behavior in "risky" animals, but stimulated risk behavior in rats that were not predisposed to it. Nicotine inhibited risk behavior in "risky" animals and strengthened it in "cautious" rats. In the intermediate group, the drugs did not induce significant changes. A similar effect of the drugs was observed in the previous models. More complex effect of nicotine on the risk behavior may be explained by the absence of severe food motivation typical for the early models.

Anxiolytic, Psychostimulant, and Analgesic Effects of Various Volumes of Ethanol Solution in Different Concentrations, but in the Same Dose.

We studied the effect of ethanol (dose 2 g/kg) in various concentrations (5, 13, and 40%) and different volumes (40, 15.5, and 5 ml/kg) on the level of anxiety, locomotor activity, and pain sensitivity in rats. Administration of 40 ml/kg water to animals was followed by a significant increase in the time spent in the open arms of the elevated plus maze. Administration of water in a volume of 5 or 15.5 ml/kg had little effect on the level of anxiety. The greater was the volume of intragastrically administered ethanol, the stronger was the anxiolytic effect. The psychostimulant and analgesic effects of ethanol were more pronounced after administration of medium volumes and intermediate concentrations of ethanol-containing solutions. Since administration of these solutions cannot produce maximum blood concentration of ethanol, we believe that the observed effects are mainly related to the direct effect of ethanol on the stomach tissue.

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. Administration of DAMGO to animals receiving caffeine in a dose of 10 mg/kg abolished the anxiolytic and psychostimulant effects of caffeine. By contrast, administration of DAMGO to rats receiving caffeine in a dose of 100 mg/kg had the anxiolytic effect. Activation of peripheral µ-opioid receptors is followed by the inhibition of the central µ-opioid system. We observed a decrease in the number of µ-opioid receptors in the midbrain and cerebral cortex and inhibition of ß-endorphin release from nerve ending of the cingulate cortex in rats. These changes are probably followed by activation of the adenosine system in the brain. Caffeine dose should be increased to achieve the effect. Therefore, the anxiolytic and stimulatory effects of caffeine in a dose of 10 mg/kg are abolished under these conditions. By contrast, the anxiolytic effect of caffeine in a dose of 100 mg/kg (not observed under normal conditions) develops after this treatment.

[Glutamatergic neurotransmitter system in regulation of the gastrointestinal tract motor activity].

The review include actual facts, demonstrating high probability of glutamatergic neurotransmitter system role in the regulation of the gastrointestinal tract motor activity. These facts suggest significant role of the glutamatergic neurotransmitter system dysfunction in forming motor activity disorders of the digestive tract, including in patients in critical condition. The analysis is based on results of multiple experimental and clinical researches of glutamic acid and other components of the glutamatergic neurotransmitter system in central nervous system and autonomic nervous system (with the accent on the enteral nervous system) in normal conditions and with functioning changes of the glutamatergic neurotransmitter system in case of inflammation, hupoxia, stress and in critical condition.

Changes in feeding behavior, locomotor activity, and metabolism in rats upon modulation of opioid receptors in the gastrointestinal tract.

We studied the role of µ-, δ-, and κ-opioid receptors of the stomach in the regulation of natural feeding behavior, metabolism, and locomotor activity of rats. Locomotor activity (number of crossed squares), food and water intake, oxygen consumption, and carbon dioxide release in animals were estimated in the standard home cage using a Phenomaster device (TSE) for 24 h at 40-min intervals. Administration of a µ-opioid receptor agonist DAMGO suppressed feeding behavior of animals in the light phase, but had little effect on locomotor activity and metabolism. Treatment with a δ-opioid receptor agonist DADLE was followed by the increase in metabolism over 24 h. These changes were accompanied by a decrease in locomotor activity during the light phase and activation of feeding behavior in the transition period. Intragastric administration of a κ-opioid receptor agonist ICI-204,448 inhibited feeding behavior, metabolism, and locomotor activity of rats only in the nighttime. These data suggest that opioid peptides produced in the stomach during food digestion play an important role in the regulation of food motivation and metabolism in rats. Various subtypes of opioid receptors probably regulate feeding behavior and metabolism of animals in different phases of vital activity.

Effect of activated peripheral κ-opioid receptors on the action of nicotine and its withdrawal in nicotine-dependent rats.

We studied the possibilities of modulating the effects of nicotine and its withdrawal in nicotine-dependent rats by peripheral injection of κ-opioid receptor agonist ICI 204,448. Injection of nicotine to rats previously treated with nicotine for 14 days reduced motor activity, suppressed metabolism, and increased food intake. In rats receiving ICI 204,448 after chronic administration of nicotine, food intake did not differ from that in control animals receiving isotonic NaCl solution. ICI 204,448 had virtually no effect on suppression of motor activity and metabolism. The rats receiving the last injection of nicotine 24 h prior to the experiment demonstrated an increase in metabolism, locomotor activity, and food intake. In these animals, ICI 204,448 completely abolished the effects of nicotine withdrawal. It was found that peripheral administration of compound ICI 204,448 did not significantly inhibit the effect of nicotine in nicotine-dependent rats, but abolished symptoms of nicotine withdrawal. It can be hypothesized that nicotine withdrawal syndrome is related to inhibition of dopamine release in the nucleus accumbens probably caused by enhanced κ-opioid activity in presynaptic terminals. Activation of peripheral κ-opioid receptors apparently suppressed (via vagal afferent pathways) central κ-opioid activity and reduced nicotine withdrawal symptoms in nicotine-dependent subjects.

[Glutamine, glutamate and citrulline concentration in blood plasma in patients in critical condition (pilot study results)].

UNLABELLED: Study objective was to evaluate and to compare glutamine, glutamate and citrulline plasma levels (Glu-p, Gl-p, Cit-p) with electrical activity indicators (EA) from the proximal small intestine in patients in critical condition (CC). MATERIALS AND METHODS: 27 patients in CC (15 women, 12 men, 70 +/- 14 years, from them "therapeutic profile" patients--12, "surgical"--15) have been surveyed and treated. At admission to reanimatology department (RD) Glu-p, Gl-p, Cit-p (by highly effective liquid chromatography), relative duodenal and jejunum EA--by peripheral electrogastrography--have been measured. Patients' 1st day general condition and 28-day survival rates in the RD were assessed by various scales. Glutamine preparations have not been administered. RESULTS: Relatively to norm Glu-p, Gl-p, Cit-p increase has not been observed. By Gl-p and Cit-p maintenance patients were classified into 2 clusters, nominally named accordingly to decreased or normal Gl-p level as glutamatergic system hypofunction condition (HCS) and glutamatergic system normofunction (NGS). HGS condition is associated with more expressed proximal small intestine EA and less 28-day RD survival (p < 0.05), the worst prognosis was observed in case of combination of more signified proximal small intestine relative EA depression with subnormal Gl-p or Cit-p less than 10 mcmol/l. CONCLUSION: HCS or NGS condition is characteristic for patients in extremely critical condition (with APACHE II 30 (24; 38)). Conjunction of glutamate (Gl) and its' biochemical metabolism indicators maintenance alterations in peripheral blood, small intestine EA parameters and 28-day survival rates in RD shows the participation of glutamatergic system in pathogenesis of functional gastrointestinal tract motor activity disorders in patients in CC, possible diagnostics courses and rationality of its hypofunction correction.

Estimation of the level of anxiety in rats: differences in results of open-field test, elevated plus-maze test, and Vogel's conflict test.

We compared individual anxiety assessed by three standard tests, open-field test, elevated plus-maze test, and Vogel conflict drinking test, in the same animals. No significant correlations between the main anxiety parameters were found in these three experimental models. Groups of animals with high and low anxiety rats were formed by a single parameter and subsequent selection of two extreme groups (10%). It was found that none of the tests could be used for reliable estimation of individual anxiety in rats. The individual anxiety level with high degree of confidence was determined in high-anxiety and low-anxiety rats demonstrating behavioral parameters above and below the mean values in all tests used. Therefore, several tests should be used for evaluation of the individual anxiety or sensitivity to emotional stress.

[Prognostic evaluation of sleep in patients in a vegetative state].

Coma in the genuine sense is a dreamlike state that lasts not more than 3 weeks, thereafter it progresses to a vegetative stage of consciousness recovery, except when a patient has died or regained conscious wakefulness. Among those who have achieved the vegetative state progress to the following stage of recovery: mal consciousness or completely return to the initial cognitive level. Others remain in a persistent vegetative state. The registered cases of the vegetative state is as high as 100 per million population (S. Ashwal et al., 1996). This patient category remains terra incognita even for interdisciplinary analysis by neurologists and reanimatologists. Nonetheless, the emotional and financial support to manage this patient category is high. In searching for prognostic criteria for the outcome of a vegetative state, the authors attempted to analyze sleep, one of the earliest phylogenetic autonomic functions. Based on the hypothesis that the cognitive status cannot be regained if sleep is not recovered, the authors conducted a polysomnographic study in 64 patients. Preserved sleep patterns were observed in 27 (96%) of 28 patients with a good outcome versus 11 (31%) of 36 patients with a poor outcome. It is concluded that it is expedient to incorporate polysomnographic monitoring into the examination protocol for patients in a vegetative state.

[The hemostatic system in traumatic subarachnoid hemorrhage in the Far North]. / Sostoianie sistemy gemostaza pri trazvmaticheskom subarakhnoidal'nom krovoizliianii v usloviiakh Krainego Severa.

It was found that in conditions of the extreme North sanation of the cerebrospinal fluid occurs later in patients with traumatic subarachnoidal hemorrhage than in the central regions of the country. In connection with this the hemostasis system was studied in 20 patients with traumatic subarachnoidal hemorrhage and 10 patients with brain tumours (control group). Patients with traumatic subarachnoidal hemorrhage showed significant hypocoagulation changes.