L. N. Muranova

Locomotor responses and neuron excitability in conditions of haloperidol blockade of dopamine in invertebrates and vertebrates.

Levels of movement activity were used to identify two groups of rats: those with high- and low-activity levels. Blockade of dopamine receptors with haloperidol led to suppression of locomotor activity in both groups of rats; in common snails, haloperidol decreased the rate of locomotion. The excitability of spinal centers in rats decreased 5 min after single i.v. injections, with gradual recovery seen by 30 min. Chronic administration of haloperidol suppressed post-tetanic potentiation of the H response in the gastrocnemius muscle of spinal rats. Prolonged use of haloperidol induced significant hyperpolarization of the membrane potential of command neurons in common snails and increased the action potential generation threshold. Selective pharmacological exclusion of the brain dopamine system was found to lead to decreases in the excitability of defined neurons in snails and the spinal motor centers in rats, also producing impairments in locomotor responses in these animals.

ESR study of the nitric oxide production in tissues of animals under an external influence on the functioning of the cardiovascular and nervous systems

Electron spin resonance (ESR) of the ternary (DETC)2-Fe2+-NO complex has been applied to determine the nitric oxide production in tissues of rats and snails. A preliminary ESR study of the NO content in tissues of rats before and after artificially induced acute myocardial infarct was performed. The analysis of the obtained results shows that the nitric oxide production during the first hour after the moment of inducing myocardial infarct decreases. It is also demonstrated that ESR may be useful in the study of the influence of the long-term sensitization of snails on the nitric oxide production in their body. The changes in the NO production after the external influences in both cases are discussed.

Changes in nitric oxide in heart of intact and sympathectomized rats of different age

Nitric oxide production in heart tissues of rats of different age in the norm and after pharmacological sympathectomy was studied by electron spin resonance spin-trapping. Rats at the age of 14, 21, 70, and 100 days were used in the experiment. The concentration of nitric oxide produced in rat heart tissues proved to considerably decrease during ontogeny. Pharmacological sympathectomy notably decreased nitric oxide production in the heart in 14-and 21-day-old rats: the nitric oxide concentration in the spin trap as well as the level of R and T conformers of hemoglobin nitrosyl complexes decreased. In 70-day-old rats, pharmacological sympathectomy had no notable effect on the level of nitric oxide-containing paramagnetic complexes.

Study of effects of antibody to protein S100 on ionic channels of input and output currents of identified neurons of the snail Helix lucorum

In the course of electrophysiological experiments, two types of the neurons of the edible snail Helix lucorum were detected, which responded by different way to application of antibodies to the neuron-specific calcium-binding S 100 protein (AS1000). Under effect of AS100, frequency of the action potential (AP) generation in the spontaneously active V1, V3, V17, and RPa6 cells decreased, whereas in V4 and V6 cells increased. On addition of quinine solution the AP generation frequency of these neurons decreased more than twice, while the AP duration (tS) rose 6 times. The combined action of AS100 and quinine did not change statistically significantly the AP generation frequency, membrane potential (MP) and AP generation threshold (APt), as compared with the effect of AS100 in saline. The value of the AP duration (tS) increased 1.6 times, which was less pronounced as compared with the quinine action in saline. This means that AS100 prevents an increase of the AP duration after the quinine application (block of the Ca-depended K-channels). The main AS100 effect at the level of the ionic currents is shown to consist in a decrease of the maximal value of the input current, on average, by 20%, while of the output current, on average, by 12%.

Effects of Preliminary Administration of Haloperidol in Low Doses on the Effects of Haloperidol on Behavioral Reactions and Command Neuron Membrane Potential in Edible Snail

We studied the effects of preliminary administration of haloperidol in low doses on changes in motor activity of edible snail and in electrical properties of defensive behavior command neurons induced by chronic administration of haloperidol. The rate of locomotion decreased after injections of haloperidol preparations (С6, С12, С30, С200 and a mixture С12+С30+С200) for 3 days. Similar changes were observed after 3 days of haloperidol administration. Haloperidol preparations in low doses produced a modulating effect on the decrease in locomotion rate and hyperpolarization of command neurons in edible snails caused by chronic exposure to haloperidol: the decrease in locomotion rate caused by chronic haloperidol treatment was prevented by preliminary injection of haloperidol in low doses С6, С12 and С30; the depolarizing shift of command neuron membrane potential was also abolished after consecutive injection of the same haloperidol preparations С6, С12 and С30.

Changes in Electrical Properties of Command Neurons during Protective Effect of Low Doses of Antibodies to S100 Protein on the Development of Long-Term Sensitization in Helix lucorum

We studied the effect of antibodies to Ca2+-binding protein S100 in a dilution of 10−12 (LATS100) on the development of long-term sensitization in Helix lucorum, a neurobiological model of anxious and depressive states. After administration of LAT-S100 preventing the development of long-term sensitization before training, the membrane and threshold potentials in command neurons regulating defense behavior decreased less markedly than during longterm sensitization. It is assumed that the “protective” effect is associated with mechanisms of long-term potential maintenance and changes in intra- and extracellular balance of Ca2+- binding protein S100.

Investigation of Changes in NO Content during Long-Term Sensitization in Edible Snail Using EPR-Spectroscopy: Effects of Antibodies to Calcium-Binding Protein S-100

EPR-spectroscopy experiments (electron paramagnetic resonance) demonstrated a decrease in NO production in the nervous system and heart of edible snail Helix lucorum after formation of long-term sensitization, a neurobiological model of anxiety and depression. The protective effect of antibodies to Ca2+-binding protein S-100 in dilution of 10−12 on the formation of long-term sensitization was accompanied by partial recovery of NO synthesis in the nervous system and heart. These findings indicate that the imbalance in Ca2+-binding protein S-100 can lead to inhibition or modulation of some processes during plastic reorganization in the body and especially during pathological processes.

Effect of Neuroleptic Haloperidol, L-DOPA Precursor Dopamine, and Neurotoxic Dopamine Analog 6-OHDA on Acquisition of Conditioned Defensive Reflex in Edible Snail

The effect of neuroleptic haloperidol, a dopamine precursor L-DOPA, and dopamine analog 6-OHDA on the development of conditioned defensive reflex was studied in edible snails. Injection of L-DOPA to intact snails and to snails pretreated with 6-OHDA 2 h before learning session decelerated acquisition of the conditioned reflex and exerted a toxic action. In contrast, injection of 6-OHDA or haloperidol did not affect acquisition of the conditioned reflex.

Electron paramagnetic resonance study of nitric oxide production during 5-HT2 receptor blockade in the blood, heart, and liver of rats with myocardial infarction

The effect of serotonin 5-HT2 receptor blockade on nitric oxide production in rats with myocardial infarction was evaluated by the method of electron paramagnetic resonance. The spectra were recorded in samples of the heart tissue (left and right chambers), liver, and blood. 5-HT2 receptor blockade during myocardial infarction was followed by a decrease in the total content of nitrosyl complexes in the spin trap and R and T conformers of Hb-NO. The percent of T conformers increased in the remaining complexes of Hb-NO. These changes were observed in the heart and, particularly, in the blood. The amount of spin-trap complexes was lower in the liver. Hence, nitric oxide molecules were primarily associated with the spin trap in liver tissue. The decrease in the number of Hb-NO complexes in the blood probably reflects the decrease in the severity of hypoxia due to myocardial infarction. A correlation was found between these changes and physiological state of rats. 5-HT2 receptor antagonist improved general state of rats with infarction and increased survival rate.

The effects of 6-Hydroxydopamine on the electrical characteristics of snail neurons in long-term sensitization

The effects of the neurotoxin 6-hydroxydopamine on the formation of long-term sensitization and changes in the membrane characteristics of identified neurons were studied. Injections of the neurotoxin 6-hydroxydopamine blocked the acquisition of long-term sensitization; when neurotoxin injections were given after the formation of long-term sensitization, they had no subsequent effect on conduction parameters. At the cellular level, recording of the electrical characteristics of common snail defensive behavior command neurons (LPa3, RPa3, LPa2, and RPa2) showed that the effects of 6-hydroxydopamine consisted of a small depolarization shift in the membrane potential and a change in the action potential generation threshold. Formation of long-term sensitization after injections of 6-hydroxydopamine did not lead to further decreases in the membrane and threshold potentials of command neurons as compared with snails only given injections of 6-hydroxydopamine. The changes in electrical measures of command neurons induced by administration of the neurotoxin 6-hydroxydopamine lasted at least two weeks.