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[Preventive effect of lithium chloride on the development in rats of a preference for ethanol].

It was revealed in experiments on rats treated with a 5% ethanol solution with equal quantities of LiCl (experiment) and NaCl (control) for seven weeks as the only source of liquid that with li+ concentration in the blood plasma of approximately 0.6 meq/1 LiCl prevented the development of alcohol dependence. On studying the neurosecretory hypothalamic nuclei, hypophysis and adrenal cortex of the same animals a certain correlation has been demonstrated between the morphofunctional condition of the mentioned formations, the degree of ethanol preference development and the character of LiCl influence on the process.

Alcoholism

Potentiating effect of lithium chloride on methamphetamine-induced stereotypy in mice.

Single administration of LiCl potentiated the methamphetamine-induced stereotypy in mice, without affecting the concentration of methamphetamine in brain. During MAO inhibition, the level of 3-methoxytyramine (3-MT), an O-methylated metabolite of dopamine, was reduced by LiCl, but the elevated 3-MT level observed after the administration of methamphetamine was not influenced by LiCl.

Animals

The effects of phenobarbital on lithium chloride induced taste aversion.

The dose related effects of phenobarbital on LiCl induced taste aversion were examined. Rats were adapted to a 23 hr 50 min water deprivation schedule. On the Treatment Day animals were offered a novel 0.125% saccharin solution during the 10 min drinking session and were then administered 3.0 mEq/kg LiCl. The saccharin solution was presented again on six subsequent Test Days. Sodium phenobarbital 20, 40, 60 and 80 mg/kg was administered 15 min prior to drinking on the first Test Day. Results indicated that all doses significantly attenuated taste aversion with the maximal effect occurring with the 60 mg/kg dose.

Animals

Thermodynamic characterization of partially denatured states in the denaturation process of bovine alpha-lactalbumin by inorganic denaturants.

In an attempt to understand the specific effect of inorganic protein denaturants, lithium cation and perchlorate anion, upon the molecular conformation of bovine alpha-lactalbumin and to characterize the denatured states of the protein and the denaturation processes, themodynamic studies on the reversible unfolding of the protein in the presence of lithium chloride, lithium perchlorate and sodium perchlorate were made by means of circular dichroism and ultraviolet absorption measurements. The denaturation reaction caused by lithium chloride was found to take place in a three-state type, while that caused by the two perchlorates in a two-state type. The latter produces the same denatured state as the acid does on the protein, the state where the helical structures remain unchanged. The former produces two kinds of the denatured state, one being a less unfolded state than the acid denatured one and the other a fully unfolded state which is identical with the finally denatured state induced by organic denaturants such as guanidinium chloride, guanidinium thiocyanate and urea.

Animals

[Spheroplasts of plague microbe strains from the Transcaucasian uplands and their capacity for pesticin synthesis].

Spherical formations of the plague microbe strains from the Transcaucasian Upland, I plague microbe strain of the sandwort variety and I strain of the marmot variety were obtained under the effect of lithium chloride. They had the remains of the cell wall, were viable, sensitive to osmotic shock, preserved sensitivity to the specific bacteriophage and pesticins. All this was evident of isolation of the spheroplasts of the plague microbe. The spheroplasts showed a capacity for pesticin production. The pesticin synthesis by the spheroplasts of the plague causative agent from the Transcaucasian Upland increased with an increase in the content of lithium chloride in the medium. The largest inhibiiton zones were observed, when 0.7-0.8 per cent of lithium chloride were present in the medium. In the spheroplasts of the plague causative agent from the Mountain Altai (the marmot variety) the pesticin synthesis was inhibited with an increase in the content of lithium chloride in the medium. The activity spectrum of the pesticins of the spheroplasts of the plague causative agent from the Transcaucasian Upland and the spheroplasts of the strains of the marmot and sandwort varieties was broader than that of the rod-like forms of these strains. The indicator properties were found in the strains of the plague microbe of the marmot and sandwort varieties with respect to the pesticins of the spheroplasts of the sel-like producing organisms and organisms from the Transcaucasian Upland.

Biological Products

Lithium administration antagonizes cholinergic behavioral effects in rodents.

Physostigmine, a centrally acting cholinesterase inhibitor, antagonizes methylphenidate-induced stereotyped gnawing behavior in mice and rats. This effect is significantly attenuated when lithium chloride is concurrently administered, indicating that lithium chloride may antagonize central cholinergic activity. This observation may have theoretical implications for an adrenergic-cholinergic balance hypothesis of affective disorders.

Animals

Inorganic salt denaturants stabilize ribonuclease against denaturation by urea.

The isothermal denaturation of ribonuclease A by mixed denaturant systems was investigated at 25 degrees C. It was observed that low concentrations of lithium chloride stabilize the protein against denaturation by urea, even though the salt itself is a denaturant. This study also provides, for the first time, the most convincing evidence that the lithium chloride denatured ribonuclease A contains some of the native secondary and tertiary structure.

Animals

The pharmacokinetics of lithium in the brain, cerebrospinal fluid and serum of the rat.

1 Addition of lithium carbonate (55 mmol/kg dry wt.) to the diet of rats for 4 days resulted in ratios between lithium in the brain and serum and between the cerebrospinal fluid (CSF) and serum of approx. 1 and 0.4, respectively. The relationships between the concentrations were linear. 2 After single intraperitoneal injections of lithium chloride (5 mmol/kg body wt.) the concentration of lithium in the CSF was greater than that of the brain for 2 h. 3 Repeated subcutaneous injections of lithium chloride (0.9 mmol/kg body wt.) resulted in steady state ratios corresponding to those observed when lithium was given in the diet. The rate of elimination from the CSF was intermediate between that of the serum and cerebral tissue until a new equilibrium was reached after approx. 24 h. At that time the ratios between lithium in the brain and serum, and in the CSF and serum were increased to approx. 5 and 0.8, respectively. 4 These results are consistent with passive transfer kinetics of lithium in the CSF and elimination of lithium from the cerebral tissue via the CSF. 5 The results may explain some of the phenomena observed in patients during intoxication with lithium.

Animals

Eliciting conditioned taste aversion by cobra venom neurotoxin in rats.

An attempt is made to study conditioned taste aversion (CTA) using cobra venom antivenom or lithium chloride as the Unconditioned Stimulus (US). Twenty-four hour water deprived rats were habituated for two consecutive days to drinking tap water in the drinking box for 15 minutes daily. On 3rd day they were allowed to drink 0.1% sodium saccharin. Thirty minutes later, they were injected with cobra venom (45 micrograms), antivenom (0.022 microliter), antivenom followed by venom, lithium chloride (0.15 M, 4% body weight) or physiological saline. After two days of recovery the animals were water deprived for twenty four hours and water intake was measured on the 7th and 8th day. Retention test on the 9th day shows reduced saccharin consumption in the lithium chloride and venom groups. CTA was significantly reduced in the antivenom-venom group and absent in the antivenom and control group. It is concluded cobra venom can induce clear-cut CTA in rats.

Animals

[Protection of a naive rat from consuming a solution by a congeneric rat which has learned to refuse it].

When a rat drinks a solution of lithium chloride, it learns once and for all to refuse solutions of similar (salty) taste. In the presence of a naive rat, rats treated with lithium chloride develop an "eviction" behaviour which makes them push the naive rat away from the saline. The result is a "protection" of the naive rat, made apparent from a fall in the consumption of the solution offered.

Animals

Emergence of interoceptive and exteroceptive control of behavior in rats.

The role of exteroceptive and interoceptive aversive stimuli in rats 2 to 14 days old was investigated according to an odor aversion paradigm. Amyl acetate odor was paired with eigher peripheral shock, intraperitoneal shock, or lithium chloride poisoning. Intraperitoneal shock was an effective unconditioned stimulus at all ages and produced odor aversions comparable to lithium chloride poisoning; peripheral shock, however, was effective only in rats 10 days of age or older. Interoceptive control of aversively motivated behaviors thus seems to develop before exteroceptive control, and the failure of previous studies to find reliable learning and retention of shock-motivated behaviors before 8 to 10 days of age may be attributable to the site to which shock was applied rather than to insensitivity to shock per se.

Age Factors

Electrical stimulation of the amygdala as a conditioned stimulus in a bait-shyness paradigm.

Animals receiving low-intensity electrical stimulation of the basolateral nucleus of the amygdala while drinking plain tap water were injected with toxic doses of lithium chloride to examine whether brain stimulation can serve as a conditioned stimulus in a bait-shyness paradigm. Subjects receiving this pairing greatly reduced their water intake in a retention test, in a similar manner to a group in which saccharin was paired with poisoning. Pairing lithium chloride with stimulation of the amygdala had no effect on subsequent water intake in the absence of brain stimulation. This effect appears to be locus specific, as caudate stimulation could not serve as a conditioned stimulus.

Amygdala

[Role of the kidneys in the pathogenesis of lithium poisoning].

Lithium intoxication was induced in rats by intraperitoneal administration of lithium chloride in a daily dose of 200 mg/kg (0.22 LD50) for 6 days. Polyuria connected with pathological changes in the epithelium of the convoluted tubules and depression of the antidiuretic hormone--acid mucopolysaccharides system in the area of the straight kidney tubules was observed on the 6th day of the experiments. Oligouria and death of some of the animals on the 7th experimental day was caused by severe lesions the kidney structure. Further observation (30 days) demonstrated that, along with the regeneration processes, there developed a marked sclerosing ofthe kidney tissue. A conclusion was drawn that severe lithium intoxication was associated with the development of acute renal insufficiency. Functional reserves of the kidneys after the cessation of lithium chloride administration remained lowered for a long period.

Acute Kidney Injury

Effects of electroshock and drugs administered in vivo on protein kinase activity in rat brain.

The effect of electroshock and treatment with reserpine, amphetamine or lithium chloride on protein kinase activity in synaptic membrane fragments prepared from rat brain was investigated. Naive rats subjected to electroshock procedures showed significant increases in both basal and cyclic AMP-stimulated activity irrespective of whether the treatment was sham, acute or chronic. These increases did not occur in animals which had been tamed by daily handling for 15 days prior to treatment, suggesting that the response was induced by the stress of an unfamiliar situation. Administration of lithium chloride and reserpine caused a small but significant increase in the stimulated activity. Doses of d-amphetamine of 5 mg/kg had no effect on either basal or stimulated activity, but higher doses (up to 15 mg/kg) resulted in a pronounced increase in both activities, which may have been related to drug-induced stress.

Animals