Influence of a Nitric Oxide Synthase Inhibitor on the Anxiolytic, Stimulating, and Analgesic Effects of Long-Term Perinatal Caffeine Exposure in Rats.

We studied the effect of inducible NO synthase (iNOS) inhibitor aminoguanidine on the behavioral effects of chronic perinatal caffeine exposure. Administration of caffeine in the prenatal and early postnatal periods led to the development of anxiolytic, stimulating, and analgesic effects. Administration of aminoguanidine attenuated the anxiolytic and stimulating effects and potentiated the analgesic effect of perinatal administration of caffeine.

Features of the Effects of Glutamatergic System Modulators in the Model of Hyperthermal Seizures in Rat Pups.

We studied the effect of lamotrigine, an anticonvulsant inhibiting the presynaptic release of glutamate, and LY341495, an antagonist of metabotropic glutamate 2/3 receptors, on the development of hyperthermic seizures and the content of LPO products in the brain of 8-10-day-old Wistar rats. Rat pups in the early postnatal period demonstrated pronounced seizures in response to thermal exposure, which was accompanied by an increase in the level of LPO products in the cerebral cortex. It was shown that the latency of generalized seizures increased after administration of both lamotrigine and LY341495.

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.

Metabotropic glutamate receptors and nitric oxide in dopaminergic neurotoxicity.

Dopaminergic neurotoxicity is characterized by damage and death of dopaminergic neurons. Parkinson's disease (PD) is a neurodegenerative disorder that primarily involves the loss of dopaminergic neurons in the substantia nigra. Therefore, the study of the mechanisms, as well as the search for new targets for the prevention and treatment of neurodegenerative diseases, is an important focus of modern neuroscience.

Age-Related Individual Behavioural Characteristics of Adult Wistar Rats.

The aim of this work was to study age-related changes in the behaviour of adult Wistar rats using the open field (OF) and elevated plus maze (EPM) tests. Behavioural changes related to motor activity and anxiety were of particular interest. Results showed that as male and female rats progressed from 2 to 5 months of age, there was a decrease in the level of motor and exploratory activities and an increase in their level of anxiety.

Role of nitric oxide in psychostimulant-induced neurotoxicity.

In recent decades, consumption of psychostimulants has been significantly increased all over the world, while exact mechanisms of neurochemical effects of psychomotor stimulants remained unclear. It is assumed that the neuronal messenger nitric oxide (NO) may be involved in mechanisms of neurotoxicity evoked by psychomotor stimulants. However, possible participation of NO in various pathological states is supported mainly by indirect evidence because of its short half-life in tissues.

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.

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 peripheral opioid receptor agonists on depressive activity of ethanol.

We studied the effect of peripheral μ- and κ-opioid receptor agonists (not crossing the bloodbrain barrier) on locomotor activity and metabolism in rats after acute administration of ethanol. Intraperitoneal injection of ethanol in a single dose of 2 g/kg had a strong depressive effect manifested in a decrease in horizontal locomotor activity and suppression of metabolism. μ-Opioid receptor agonist DAMGO and κ-opioid receptor agonist ICI 204,448 partly abolished the effect of ethanol on locomotor activity of rats.

Effect of peripheral D₂ dopamine receptor antagonist domperidone on metabolism, feeding behavior, and locomotor activity of rats.

We studied the possibility of activation of the central dopaminergic system compartment by modulating activity of D2 dopamine receptors in the gastrointestinal tract with domperidone, an antagonist not crossing the blood-brain barrier. Intragastric administration of 0.1 mg/kg domperidone to rats was followed by a significant decrease in feeding behavior and stimulation of basal metabolism, but had no effect on locomotor activity of animals in a Phenomaster system.

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%).

Loperamide effects on anxiety level and feeding behavior in rats. Role of vagal afferentation.

We investigated the role of vagal afferentation in the interaction of the peripheral and central parts of the endogenous opioid system, in the mechanisms of sensorial satiation and anxiety in rats. It has been established that vagotomized rats spent less time in open arm of the plus-maze in comparison with sham-operated animals. Peripheral administration of μ-opioid receptor agonist loperamide was shown to reduce anxiety level in sham-operated rats and had no effect on this parameter in vagotomized animals.

Role of metabotropic glutamate receptors in the mechanisms of experimental parkinsonism development.

We studied the effects of metabotropic glutamate receptor 5 (mGluR5) antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) on the development of catalepsy and NO generation in the striatum of rats under conditions of long-term treatment with low doses of rotenone, a mitochondrial complex I inhibitor. In rats receiving single intraperitoneal injection of rotenone (1.5 mg/kg), NO concentration in the striatum did not differ from that in animals receiving sunflower oil.

Effect of peripheral administration of peptide ligands of δ-opioid receptors on anxiety level and locomotor activity of rats.

We studied the effect of intragastric administration of a peptide δ-opioid receptor agonist DADLE and peptide δ-opioid receptor antagonist ICI 174.864 on anxiety and locomotor activity of rats. Peripheral administration of ICI 174.

Changes in feeding behavior after peripheral loperamide administration in rats.

Changes in the parameters of operant feeding behavior and body weight were studied in rats after intragastric administration of μ-opioid receptor agonist loperamide. Loperamide administration significantly suppressed foraging behavior in rats and reduced their body weight. Our findings suggest that peripheral loperamide administration, according to the hypothesis of reciprocal interactions between the central and peripheral parts of the endogenous opioid system, suppresses activity of central opioid mechanisms of feeding behavior organization.

[Central and peripheral mu-opioid systems in the mechanisms of emotional stress].

The aim of the work was to study effect of peripheral administration of mu-opioid receptor ligands unable to penetrate through the hematoencephalic barrier on the measures of emotionality in rats and on the release of beta-endorphins from nerve endings of the anterior cingulate cortex during emotional stress. The mu-opioid receptor agonist loperimide mostly acted as an anxiolytic whereas the receptor antagonist methylnaloxon showed depressive activity. Lifetime microdialysis and subsequent immunoenzyme assay demonstrated that intraventricular infusion of loperamide and methylnaloxon decreased and increased respectively the surge of beta-endorphin into the intercellular space.

Peripheral administration of loperamide and methylnaloxone decreases the degree of anxiety in rats.

We studied the effect of μ-opioid receptor ligands on anxious and depressive behavior of rats. Intragastric administration of loperamide and methylnaloxone reduced animal anxiety evaluated by an increase in the number of entries into and time spent in open arms of the elevated plus-maze. μ-Opioid receptor agonist loperamide had the most pronounced anxiolytic effect.

Modulation of peripheral opioid receptors affects the concentration of mu-opioid receptors in rat brain.

Radioligand binding assay was used to evaluate characteristics of central mu-opioid receptors after peripheral administration of mu-opioid receptor agonist loperamide and antagonist methylnaloxone. These substances do not cross the blood-brain barrier. Loperamide and methylnaloxone produced opposite effects on the density of mu-opioid receptors in the frontal cortex of rat brain.

Antagonist of M1 muscarinic acetylcholine receptor prevents neurotoxicity induced by amphetamine via nitric oxide pathway.

The psychostimulant amphetamine (AMPH) has been found to induce striatal acetylcholine release and neurotoxic processes via nitric oxide (NO) and lipid peroxidation (LPO). Our purpose was to determine whether blocking striatal muscarinic (M1) receptors by the selective M1 antagonist toxin 7 (MT 7; bilaterally, 2 microg per side) might attenuate the effects of AMPH (4 x 5 mg/kg, i.p.

Nitric oxide and oxidative stress in the brain of rats exposed in utero to cocaine.

The role of nitric oxide (NO) and lipid peroxidation (LPO) processes in the physiological deficits induced by in utero cocaine exposure was examined in rats. NO generation in the hippocampus and cortex was detected using the electron paramagnetic resonance and LPO products were measured as thiobarbituric acid reactive species (TBARS). Pregnant Sprague-Dawley rats received a daily intraperitoneal injection of 20 mg/kg cocaine (IUC) or saline solution for control dams (IUV) between E17-E20.

Modulating role of NO in haloperidol-induced catalepsy.

Injection of haloperidol during catalepsy modeling decreased the content of NO in rat cerebral cortex. NO precursor L-arginine arrested catalepsy and prevented the decrease in NO content.

Memory impairments and oxidative stress in the hippocampus of in-utero cocaine-exposed rats.

We examined whether significant oxidative stress is induced in the brain of juvenile rats exposed in utero to cocaine, and contributes to their mnesic difficulties. We measured nitric oxide generation, using electron paramagnetic resonance, and the thiobarbituric acid reactive species as specific indexes of lipid peroxidation. Both nitric oxide and lipid peroxidation were elevated in the hippocampus of in-utero cocaine-exposed rats as compared with control animals.

Comparative effects of NO-synthase inhibitor and NMDA antagonist on generation of nitric oxide and release of amino acids and acetylcholine in the rat brain elicited by amphetamine neurotoxicity.

The aim of this study was to clarify the role of nitric oxide (NO) and lipid peroxidation (LPO) processes as well as the contribution of various neurotransmitters in pathophysiological mechanisms of neurotoxicity induced by amphetamine (AMPH). NO level was determined directly in brain tissues using electron paramagnetic resonance spectroscopy technique. The content of the products of lipid peroxidation (LPO) was measured spectrophotometrically as thiobarbituric acid reactive species (TBARS).

7-nitroindazole, nNOS inhibitor, attenuates amphetamine-induced amino acid release and nitric oxide generation but not lipid peroxidation in the rat brain.

The aim of the present study was to elucidate whether amphetamine modulates the output of the neurotransmitters glutamate, aspartate, GABA and acetylcholine (ACh) in nucleus accumbens (NAc) as well as the formation of lipid peroxidation (LPO) and nitric oxide (NO). D,L-amphetamine (AMPH, 5 mg/kg, i.p.

Chronic administration of rotenone increases levels of nitric oxide and lipid peroxidation products in rat brain.

The complex I inhibitor rotenone is a neurotoxin that has been proposed to induce Parkinson-like degeneration. As the mechanisms of rotenone toxicity are not fully understood, the present study addresses the question of whether rotenone induces NO production and lipid peroxidation-like products, that is, thiobarbituric acid reactive substances (TBARS). Rotenone at a dose of 1.