Effects of lithium salts on experimental neurogenic lesions of the stomach and heart

It has been demonstrated in experiments on noninbred rats that lithium chloride and lithium hydroxybutyrate exert a prophylactic therapeutic effect in respect to neurogenic gastric lesions and reduction in the content of creatine phosphate in gastric and cardiac tissues, induced by stressful exposures (3-hour immobilization and electric stimulation of hungry animals). The effects of lithium hydroxybutyrate were more demonstrable than those of lithium chloride.     

Effect of lithium preparations on cardiac arrhythmias due to strophanthin in waking rats

It was shown in experiments on conscious rats that intravenous injection of strophanthine in toxic doses provokes heart arrhythmias and death of the animals. Lithium drugs (lithium chloride and lithium hydroxybutyrate) injected during arrhythmias led to a short-lived effect of heart rhythm normalization. Lithium hydroxybutyrate was more effective if administered shortly after strophanthine injection, reducing the latter's cardiotoxic effect and preventing the death of the majority of the animals.     

Effects of lithium hydroxybutyrate on circadian rhythm of rest-activity and sleep structure in experimental animals]

Lithium hydroxybutyrate (10 mg/kg, 10 days) influences circadian temperature and activity rhythms of rats in "open field" and sleep structure according to the time of preparation of the injection (8.30 or 19.30). It was stated that lithium hydroxybutyrate modified circadian rhythms and sleep structure less after morning injections into the rats, while evening administration destabilized circadian rhythms, increased slow-sleep and decreased REM sleep duration.     

Effect of lithium preparations on the toxic effects of adrenaline

Experiments on rats have shown that intravenous injection of adrenaline in a dose of 0.3-0.4 mg/kg causes cardiac arrhythmia. In this case the primary arrhythmia developing immediately after adrenaline injection is followed by the recovery of sinusal rhythm which was replaced by the secondary arrhythmia. Apart from arrhythmias, there developed pulmonary edema. The animals died 2--3 minutes after adrenaline injections. Lithium chloride and lithium hydroxybutyrate removed the secondary arrhythmia and pulmonary edema. Lithium hydroxybutyrate has proved to be more effective.     

Effect of lithium oxybutyrate on the serotonin and 5-hydroxyindoleacetic acid content in the brain of rabbits

Single administration of lithium hydroxybutyrate (10 mg/kg) to rabbits decreased serotonin and 5-hydroxyindoleacetic acid (5-HIAA) content in the caudate nucleus. The drug administration for 8 days is accompanied by mediator accumulation in the cortex, caudate nucleus, tonsils, hypothalamus, thalamus, and midbrain with parallel reduction in 5-HIAA level in these structures. 15 days of lithium hydroxybutyrate administration lead to the increase of serotonin and 5-HIAA concentration, while 28 days of administration reduced the content of mediator and its metabolite.     

Effect of lithium salts on neuropathological syndromes of spinal origin

Experiments on noninbred rats were made to study the influence of lithium hydroxybutyrate on two patterns of spinal cord pathology: the generalized myoclonus and painful syndrome of spinal origin. The syndromes were induced by generators of pathologically enhanced excitation in the ventral and dorsal horns of the spinal cord. The effects of lithium chloride and sodium hydroxybutyrate were examined to compare the influence of lithium (cation) and hydroxybutyrate (anion) components to elucidate the role of each of the components. Lithium hydroxybutyrate appeared more effective, since it inhibited the generator of pathologically enhanced excitation in the appropriate structures, provoking the anticonvulsant effect in myoclonus and suppressing the painful syndrome.     

Protective effect of lithium oxybutyrate on the ischemic myocardium

In the experiments on different animal species (mice, cats, dogs) lithium hydroxybutyrate has been shown to have antihypoxic and anti-ischemic effects. Lithium hydroxybutyrate improved the functional state of the ischemic myocardium, stimulated the accumulation of macroergic phosphates (ATP) in the heart, protected the ischemic myocardium and delayed the progression of the reversible ischemic damage into the irreversible one. The improvement of the collateral coronary circulation plays an important role in the anti-ischemic action of the drug.     

Prophylactic effects of sodium oxybutyrate and lithium oxybutyrate on stress-induced depression of the activity of normal killers in mice

The possible use of sodium hydroxybutyrate and lithium hydroxybutyrate for the prevention of the decrease in splenic natural killer activity has been studied in CBA mice upon 6-hour immobilization stress. Both agents proved to be effective in preventing stress-induced depression of NK activity. However, a protective effect of lithium hydroxybutyrate was observed at a dose 4 times lower than that of sodium hydroxybutyrate.     

Combined action of lithium salts and serotonin on the caudate nucleus

Intracaudate injections of lithium hydroxybutyrate (5 micrograms) produce a serotonin-like effect on the power characteristics of the caudatogram frequency ranges. However, when injected in a single dose, the drug is a serotonin antagonist at the level of the caudate nucleus. On the contrary, being administered for a long time, the drug potentiates the action of the mediator.     

Protective action of antioxidant preparations on the development of experimental allergic encephalomyelitis in guinea pigs

The authors studied the action of combined tocopherol, lithium hydroxybutyrate and pyridoxal phosphate on the development of experimental allergic encephalomyelitis (EAE) in guinea-pigs. The use of the combined drug from the first days of immunization with encephalitis-inducing material prevented the development of EAE, activation of lipid peroxidation (LPO), and the appearance of the blood serum neurotropic activity. Administration of the combined drug starting from the 7th day after immunization appeared ineffective as was the administration of each drug alone, starting from the first days of immunization. The data obtained support an important role of LPO activation for the pathogenesis of the neuroallergic process.     

Redistribution of myocardial blood flow in chronic ischemia under the effects of pharmacological agents

In the experiments with anesthetized dogs under chronic myocardial ischemia the effect of propranolol, diltiazem, lithium and sodium hydroxybutyrate on the myocardial blood flow redistribution was studied with the help of ultrasonic method. The redistribution was estimated by the ratio change of blood flows in veins which drain blood directly from the focus of myocardial ischemia and total myocardial of left ventricular (v cardiac magna). It was established that propranolol increases the ratio and diltiazem decreases it. Some differences in the effect of antihypoxic drugs were revealed. Sodium hydroxybutyrate redistributed the blood flow in favour of the focus of myocardial ischemia and lithium hydroxybutyrate increased the blood flow both in the focus of myocardial ischemia and in the conditionally-intact region of myocardium of left ventricular.     

Comparative study of several preparations in different models of cerebral hypoxia

The antihypoxic effects of gutimine, piracetam, sodium hydroxybutyrate and lithium hydroxybityrate were studied on different models of brain hypoxia. All the drugs under study produced a remarkable antihypoxic effect in experimental asphyxic hypoxia, increasing brain resistance to oxygen deficiency and rapidly restituting brain function. Drug pretreatment of the animals with carotid artery occlusion raised the number of animals which survived 24 h after the operation. GABA salts appeared the most effective. Sodium hydroxybutyrate increased the lifespan of rats under histotoxic hypoxia.     

The role of low sodium ion concentrations in the generation of action potentials by neurons of the apple snail (Helix pomatia)

We conducted a comparative investigation of the restorative action of different sodium ion concentrations on generation of action potentials by apple snail neurons of the central nervous system kept for a prolonged period in a solution in which such ions were lacking. Of the 180 neurons investigated, 60% of the cells had lost all excitability, while 40% retained the ability to generate action potentials of normal amplitude. In neurons that ceased under these conditions to generate action potentials both independently and as the result of direct stimulation, amplitude of the action potentials and of the "overshoot" was restored after adding only 2.5–10 mM of sodium to the solution. Analogous concentrations of lithium ions did not exert a similar restorative action. They repressed the capacity of a neuron to regain excitability in the presence of small amounts of sodium ions. Increasing the external concentration of sodium after restoration of the action potentials led to a proportional decline of their amplitude. Keeping neurons in a sodium-containing solution for periods of 25 min and more caused restoration of the neuron's ability to increase linearly the amplitude of action potentials upon raising the external concentration of sodium ions.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 3, pp. 315–322, November–December, 1969.     

Lithium does not synergize the peripheral action of cholinomimetics as seen in the central nervous system

Lithium is known to synergize the action of cholinomimetics in the CNS such that pilocarpine induces seizures in low concentration (1/13th of per se dose) in rats. The present study was undertaken to see if lithium priming also enhances the peripheral effects of acetylcholine and pilocarpine i.e. change in blood pressure in rats and contractions of the isolated guinea pig ileum. In anaesthetized rats the blood pressure was recorded from cannulated carotid artery connected through the pressure transducer to Coulbourn polygraph. The blood pressure response of pilocarpine was not different either in magnitude or in duration when administered 1, 2 and 4 h after lithium chloride (3 meq/kg) pretreatment as compared to the control. Similarly acetylcholine effect remained unchanged after lithium chloride priming. In the isolated guinea pig ileum experiments, ileum was incubated for 1 h in different concentrations of lithium chloride and effect on acetylcholine induced contractions were observed. Lithium in concentration of 2.8 x 10(-3) M had no effect on acetylcholine induced contractions while incubation with higher concentrations of 1.4 x 10(-2) M and 2.8 x 10(-2) M significant inhibition of acetylcholine contractions were observed. At this concentration, histamine induced contractions were also inhibited. The results indicate that lithium does not synergize the action of cholinomimetics in the periphery as that seen in the CNS. The inhibition of acetylcholine and histamine induced contractions in guinea pig ileum at high concentration of lithium seems to be non-specific effect.     

Dissociative state in rats induced by ethanol and possibilities of the pharmacological correction of this phenomenon

It was shown that a state of dependent learning (SDL) developed in response to ethanol (1.2 g/kg) during experimental learning of rats in conditions of T-maze. Piracetam, lithium hydroxybutyrate, litonit and new oxypyridine derivative 3-OP given in combination with ethanol prevented the development of SDL and reduced an already formed SDL. The above-mentioned combinations made the learning more difficult. It is assumed that changes in the activity of dopaminergic system, as well as membranotropic and antioxidant effects of the investigated drugs play the most important role in the mechanisms of SDL reduction.     

Dynamics of carrageenin-induced inflammation after use of lithium oxybutyrate

Lithium hydroxybutyrate (200 mg/kg) has been shown to depress the development of carrageenan inflammation. Subcutaneous drug injection in chronic inflammation of the mucous membrane in the hamster cheek pouch restored the blood flow, checked dilatation of the blood vessels, decreased their permeability and prevented necrosis of the mucous membranes. Subcutaneous drug injection depressed all the signs of both phases of acute inflammatory reaction in the rat hind foot and promoted preservation of the hind foot function. Therefore, lithium hydroxybutyrate may be an effective preparation for the treatment of inflammation.     

Indices of acute inflammation against a background of lithium oxybutyrate action

The experiments on rats have shown that intraperitoneal administration of silver nitrate solution induces peritonitis while subplantar histamine, serotonin and prostaglandin E2 administration leads to an acute paw edema. Preliminary subcutaneous injection of lithium hydroxybutyrate prevents the development of inflammation.     

Antenatal prevention, using lithium oxybutyrate, of changes in the development of the rat brain caused by serum from schizophrenic patients

It has been found that antenatal administration of schizophrenic patients' sera to rats has neuroembryotoxic effect on their progeny, decreasing the number of females in the brood, disturbing motor coordination and space perception in young male rats, slightly stimulating muscular force and motor activity, altering lateralization of the behaviour. Antenatal lithium hydroxybutyrate was shown to prevent some of the serum effects.     

The site of action of lithium ions in morphogenesis of Lymnaea stagnalis analyzed by secondary ion mass spectroscopy

Abstract. Exogastrulation as a disturbance of development in eggs of Lymnaea stagnalis is caused by the action of LiCl at the second cleavage stage and not at the first or third. The percentage of exogastrulae formed is strongly concentration dependent. To determine the site of action of lithium ions, the cellular contents of Li, C, Na, Mg, P, K, and Ca were analyzed by secondary ion mass spectroscopy (SIMS). The mean elemental concentrations of Na, Mg, K, and Ca are close to those found earlier by electron probe microanalysis and atomic absorption spectroscopy. Lymnaea eggs at the first, second, and third cleavage stage were treated with LiCl in a series of concentrations ranging from 50 to 0.1 mM. In all cases the cells contained a few mM lithium after treatment. After treatment at the insensitive first cleavage stage the lithium content is carried over by the cells through the sensitive second cleavage to the insensitive third cleavage stage. These data allow the conclusion that it is the external lithium concentration which is responsible for the specific effect. This presents direct analytical evidence that the primary action of lithium ions is located at the cell membrane.     

Efficacy of lithium hydroxybutyrate in reserpine depression

Long-term administration of lithium hydroxybutyrate (10 mg/kg, for 7 days) prevents the depression of avoidance behavior in rats and EEG alterations in the cortex and subcortical structures of rabbit brain induced by a single injection of 0.125 mg/kg reserpine.