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Effects of ovariectomy, castration, and chronic lithium chloride treatment on stereotyped behavior in rats.

The effects of ovariectomy, castration, and chronic lithium chloride treatment on stereotyped behavior (SB) induced by apomorphine (APO) (0.3--0.6 mg/kg) were investigated in rats. Duration of stereotyped behavior (interval between APO injection and termination of SB) increased in ovariectomized rats compared to female control rats. Castration had no effect on the duration of stereotyped behavior. On the other hand, ovariectomized rats that were treated chronically with LiCl (2mEq/kg daily) showed no difference in duration of stereotyped behavior compared to female controls chronically treated with LiCl. Neither treatment group showed a significantly altered intensity of stereotyped behavior compared with the appropriate control. These findings are consistent with the hypothesis that estrogen deficit contributes to a greater incidence of neuroleptic-induced tardive dyskinesia in postmenopausal women than in men of comparable age. Furthermore, LiCl may attenuate the symptoms associated with increased postsynaptic dopamine receptor sensitivity following ovariectomy.

Animals↗

Disruption of conditioned taste aversion by ECS: the role of lithium chloride.

Rats were taught a conditioned taste aversion (CTA) by pairing a 10% sucrose solution (CS) with lithium chloride (LiCl)-induced poisoning (UCS). The CS-UCS interval was 30 min. The LiCl dose (20 ml/kg) was either strong (0.15 M) or weaker (0.075 M). Electroconvulsive shock (ECS) (80 mA for 600 msec) was interpolated within the CS-UCS interval at either 15 or 30 min. ECS caused a significant disruption of CTA only when the aversion was established with the weaker dose of LiCl. There was also no indication that interference with CTA was dependent upon close temporal contiguity between the ECS and LiCl. In a second experiment a CTA was established with LiCl (0.15 M) which was heated to 45 degrees C. Under these conditions ECS produced a similar disruption of learning to that when the UCS was the weaker dose of LiCl (0.075 M). The results suggest that an apparent differential loss of learning within the CS-UCS interval described in a previous report was accidentally created when some groups of animals were poisoned with warm and others with cold LiCl.

Animals↗

The painlike effect of gallamine and naloxone differs from sickness induced by lithium chloride.

In rats, the conditioned place and taste aversions produced by 31.8 mg/kg lithium chloride were compared with those produced by 10 mg/kg gallamine in Experiment 1 and 20 mg/kg or 2.5 mg/kg naloxone in Experiments 2 and 3, respectively. Lithium produced stronger taste aversions than gallamine or the two doses of naloxone, but gallamine and naloxone each produced stronger place aversions than lithium. These findings support the distinction between two kinds of drug-induced aversive effects, having different associative properties. One effect, called sickness, is more associable with taste than with place cues; the second effect is, like pain, more associable with place than with taste.

Animals↗

In vitro effect of lithium chloride on interleukin-15 production by monocytes from IL-breast cancer patients.

Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chemotherapy for cancer. Interleukin-15 (IL-15) is a cytokine which possesses promoting activities on hematopoiesis and is also involved in antitumor response, activating NK, CTL and LAK cells. In this study we analyzed IL-15 production by monocyte cultures treated with lithium chloride (LiCl). Monocytes were obtained from patients affected by non-metastatic and metastatic breast cancer. LiCl treatment induced IL-15 production by monocytes mainly from non-metastatic patients. Combined lipopolysaccharide/LiCl treatment of monocyte cultures up-regulated IL-15 release compared to those treated with LPS alone (p<0.0001). The modulation of LiCl-induced IL-15 could counteract the immunosuppression state of cancer patients, which should be taken into account when developing new immunotherapeutic strategies.

Aged↗

Effect of lithium chloride on the palisade layer of the Triton-X-100 micelle: two sites for lithium ions as revealed by solvation and rotational dynamics studies.

Dynamic Stokes' shift measurements using coumarin 153 as the fluorescence probe have been carried out to explore the effect of added electrolyte, lithium chloride (LiCl), on solvation dynamics in the Triton-X-100 (TX-100) micelle and thus to understand the changes in micellar Palisade layer, especially the entrapped water structures in the Palisade layer. At all concentrations of LiCl, the spectral shift correlation function shows biexponential decay. At lower LiCl concentrations, the longer solvation time is seen to decrease, although the shorter solvation time is not affected much. At higher LiCl concentrations, both longer and shorter solvation times increase with electrolyte concentration. The present observations have been rationalized assuming two possible modes of interaction of the Li+ ions in the micellar palisade layer. For LiCl concentrations below about 1.5 M, the Li+ ions appear to bind preferably to the ether groups of surfactant molecules, and the increased micellar hydration with the added salt effectively makes the solvation dynamics faster. At higher LiCl concentrations, available ether binding sites for the Li+ ions seem to get occupied effectively and the excess Li+ ions start remaining in the Palisade layer as strongly hydrated free ions. Because of strong hydration of the Li+ ions, the mobility of the entrapped water molecules in the micellar Palisade layer decreases significantly, causing the solvation dynamics to slow at higher LiCl concentrations. The fluorescence anisotropy results in the present systems are also in support of the above inferences drawn from solvation dynamics results. The present results with LiCl salt are found to be substantially different than those obtained in our earlier study (Kumbhakar et al. J. Phys. Chem. B 2005, 109, 14168) with salts such as NaCl, KCl, and CsCl. These differences are attributed mainly to the binding of the Li+ ions with the surfactant ether groups, which seems to be unlikely for the other alkali cations.

Journal Article↗

Preparation of ribosome-free membranes from rat liver microsomes by means of lithium chloride.

1. Treatment of washed rat liver microsomes in a medium containing 0.12m-sucrose, 12.5mm-potassium chloride, 2.5mm-magnesium chloride and 25mm-tris-hydrochloric acid buffer, pH7.6, with 2m-lithium chloride at 5 degrees for 16hr. leads to the formation of membranes free of ribosomes and ribosomal subunits. 2. Confirmation of the absence of ribosomes from lithium chloride-prepared membranes was obtained by treatment of the membranes with sodium deoxycholate, followed by sucrose-density-gradient centrifugation, which showed the complete absence of ribosomes. 3. Treatment of membranes with phenol, followed by sucrose-density-gradient analysis of the isolated RNA, showed the presence of a small amount of 4s material. Repetition of the phenol extraction procedure in the presence of liver cell sap as a ribonuclease inhibitor again showed the presence of only 4s material. The 4s RNA was shown to be transfer RNA by the fact that it had the same capacity for accepting (14)C-labelled amino acids as isolated transfer RNA from rat liver pH5 enzyme. 4. Analysis showed that microsomes and membranes possessed similar glucose 6-phosphatase, NADH-2,6-dichlorophenol-indophenol reductase, NADH-neo-tetrazolium reductase, NADH-cytochrome c reductase and ribonuclease activities. 5. (3)H-labelled ribosomal RNA binds to membranes. However, isolation of the bound RNA by the phenol extraction procedure, followed by sucrose-density-gradient analysis, shows the RNA to be degraded to 7s material. Very little breakdown of (3)H-labelled ribosomal RNA bound to membranes occurs if the binding and isolation are carried out in the presence of liver cell sap.

Animals↗

Modulation of cell-mediated immunity by lithium chloride.

Immunomodulation of cell-mediated immunity was studied in mice treated with either lithium chloride (LiCl), anti-CD8 monoclonal antibody or their combination. While 6-day LiCl treatment decreased the ability of their splenocytes to induce a local graft-versus-host reaction--anti-CD8 abolished this effect. The proliferative response of spleen cells from those three groups of mice to concanavalin A stimulation in vitro was significantly increased. The natural killer (NK) cell toxicity of the mice was decreased by over 43% after the 6-day LiCl treatment, but was x 2.5 higher then the control value after a longer 21-d treatment. These results indicate that the immunomodulatory capacity of lithium is dependent on the type of cell population studied, and on the schedule of administration.

Animals↗

Effect of lithium chloride on spermatogenesis and testicular steroidogenesis in mature albino rats: duration dependent response.

Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle, namely type-A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7 Sd) along with Leydig cell nuclear area (LCNA) and radioimmunoassay of plasma levels of gonadotropins (FSH and LH), prolactin (PRL) and testosterone (T), activities of testicular, delta 5-3 beta hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were measured in mature rats of the Wistar strain following treatment with lithium chloride at a dose of 200 ug/100 g body wt/day for 7,14 and 21 days. A remarkable reduction in plasma levels of FSH (P less than 0.001), LH (P less than 0.05, P less than 0.01), PRL (P less than 0.05, P less than 0.001) and T (P less than 0.001) along with significant diminution in the activities of testicular delta 5-3 beta-HSD (P less than 0.001) and 17 beta-HSD (P less than 0.001) were observed following lithium treatment for 14 and 21 days. 21 days of treatment also resulted a marked degree of degeneration of ASg (P less than 0.05) and 7Sd(P less than 0.001) at stage VII but 14 days of treatment did not exhibited any significant effect on testicular gametogenesis. LCNA was decreased after lithium chloride treatment for 14 and 21 days (P less than 0.001). 7 days of treatment did not exert any notable result in the above parameters. The results of our experiment suggest that duration of lithium treatment is the critical factor for its adverse effects on testicular activity when the plasma levels of lithium remain within the therapeutic range. The possibility of an indirect action of lithium at the level of the testes is also discussed. Hence the data of our experiments have potential clinical implication.

17-Hydroxysteroid Dehydrogenases↗

[Biochemical changes in a decrease in the voluntary consumption of alcohol by rats due to lithium chloride].

A decrease of alcohol intake by ethanol-preferring rats under free choice conditions after intraperitoneal administration of lithium chloride (35 mg/kg) was accompanied by an activation of aldehyde dehydrogenase in the brain stem, a decrease of dopamine and salsolinol levels in the striatum and normalization of 11-hydroxycorticosteroids contents in the blood and adrenal glands.

11-Hydroxycorticosteroids↗

Systemic lithium reabsorption from lithium-chloride-coated heat and moisture exchangers.

OBJECTIVE: To evaluate possible reabsorption and systemic effects of lithium released by lithium-chloride-coated heat and moisture exchangers (HMEs) during prolonged mechanical ventilation. DESIGN: Prospective study, including all patients mechanically ventilated for 5-30 days. SETTING: A 7 bed general-traumatological ICU in a University Hospital. PATIENTS: 27 consecutive ICU patients, admitted following trauma, neurosurgery and respiratory insufficiency, mechanically ventilated for at least 5 days, with a lithium coated hygroscopic HME in the circuit. MEASUREMENTS AND RESULTS: Serum lithium levels were measured daily, with a standard laboratory spectrophotometric method, from admission to discharge from the ICU, and showed a reabsorption of lithium in all the patients; in the adults, levels were 5 to 15 times lower than therapeutic range, while in a child therapeutic and even toxic levels were reached. CONCLUSIONS: LiCl coat enhances HMEs' performance greatly, but reabsorption and systemic action must be considered. In adults, serum lithium levels were lower than the therapeutic range, but lithium is effective at low concentrations and it has a narrow therapeutic range; moreover, toxicity can be observed within this range too. In children, the risk of toxicity is much greater. When lithium coated HMEs are used, the risk/benefit ratio between good performance and systemic reabsorption must be evaluated carefully.

Absorption↗

Discriminative stimulus properties of lithium chloride in rats.

1. Adult male rats were trained to discriminate between an injection of lithium chloride (56 or 75 mg/kg) and saline in a two-lever operant chamber during a 20-minute session. 2. On training days, responding on the designated lever was reinforced under a fixed-ratio 20 (FR 20) schedule of food presentation, whereas responding on the other level had no programmed consequences. 3. Generalization testing with LiCl (10-100 mg/kg) was conducted after each subject reached a criterion of nine of ten sessions where 95% of overall responding occurred on the designated lever, and fewer than twenty responses were made on the other lever before presentation of the first reinforcer. 4. Substituting both lower and higher doses produced decreases in responding on the LiCl-appropriate lever while only higher doses decreased overall response rate. 5. Following generalization tests, animals were divided into two groups and varying doses of LiCl were given in combination with intraperitoneal injections of either dexamethasone (1 and 3.2 mg/kg) or ondansetron (0.32 and 1 mg/kg). 6. At doses that had little or no effect alone, neither ondansetron nor dexamethasone pretreatment blocked the discriminative stimulus properties of LiCl. 7. This research shows that LiCl can act as a highly discriminable stimulus in an operant drug-discrimination paradigm and suggests that the stimulus properties of LiCl do not derive from either direct activation of serotonin type-3 receptors or release of adrenocorticotropic hormone.

Animals↗

The effect of lithium chloride on renal structure and sodium-potassium-adenosine triphosphatase activity in dogs.

Lithium chloride was given intraperitoneally to dogs at a dosage of 125 mg/kg body weight for three days. Kidneys were removed for morphologic examination and quantitation of sodium-potassium-adenosine triphosphatase (Na-K-ATPase) activities in cortical and medullary tissue. Light microscopy showed no changes in the kidneys, but cytoplasmic vacuolation and dilatation of the cisternae of the endoplasmic reticulum were seen ultrastructurally in the epithelial cells of the distal tubule and cortical and medullary collecting ducts. Mean cortical Na-K-ATPase activity was 1.49 +/- 0.25 and 1.70 +/- 0.31 mumoles inorganic phosphate/mg protein/hour in control and experimental groups respectively. Mean medullary Na-K-ATPase activity was 4.71 +/- 0.41 and 5.01 +/- 0.47 mumoles inorganic phosphate/mg protein/hour in control and experimental groups respectively. It was concluded that lithium produced morphologic changes in the distal nephron, but had no effect on renal Na-K-ATPase activity.

Aldosterone↗

Lithium chloride stimulates human monocytes to secrete tumor necrosis factor/cachectin.

The purpose of this study was to examine the effect of lithium chloride (LiCl) on human monocytes. Patients undergoing lithium therapy have elevated white blood cell counts. Since both tumor necrosis factor alpha (TNF alpha) and interleukin 1 (IL-1), which are secreted by monocytes, can stimulate endothelial cells to produce granulocyte-macrophage colony-stimulating factor (GM-CSF), we determined whether lithium-stimulated monocytes produced TNF alpha and/or IL-1. Normal human monocytes were incubated for 24 h with medium (negative control), lipopolysaccharide (positive control), or LiCl (0.05-50 mM). The supernatants were removed and assayed for IL-1 and TNF alpha secretion using the D10.G4.01 and L929 assays, respectively. Lithium did not stimulate IL-1 secretion but did stimulate TNF alpha secretion (5-10 U/ml of TNF alpha per 2 x 10(5) monocytes). The increased secretion of TNF alpha was associated with a fourfold increase in TNF alpha mRNA. TNF alpha activity in the supernatants was neutralized by a monoclonal antibody against human TNF alpha but not by antibody against human albumin. Other alkali metals such as rubidium and cesium did not stimulate monocytes to secrete TNF alpha. These data indicate that one mechanism by which Li may cause granulocytosis is through a transcriptional enhancement of TNF production and subsequent secretion by monocytes.

Chlorides↗

Acute infusion of lithium chloride raises blood pressure in the conscious rat.

The effects of acute infusion of lithium chloride (LiCl) were studied on mean arterial pressure (MAP) and magnocellular activity as shown by the concentrations of vasopressin-associated neurophysin ([VP-RNP]) and concentrations of oxytocin-associated neurophysin ([OT-RNP]) in plasma in conscious Long-Evans rats. Chronically-cannulated rats were infused intravenously at 10 microliter/100 g body wt/min with 13% LiCl for 20 min (total dose = 6.16 mequiv./kg body wt) or 0.65% LiCl for 60 min (total dose = 0.92 mequiv./kg body wt). Effects of 13% LiCl on mean arterial pressure were also examined in vasopressin-deficient homozygous Brattleboro rats. For Long-Evans rats, infusion of 13% LiCl produced rapid and significant (P less than 0.001) increases in mean arterial pressure, the concentration of lithium in plasma ([Li+]), plasma osmolality (Posmol), [VP-RNP], [OT-RNP] and significant decreases in heart rate and sodium concentration in plasma ([Na+]). For similar changes in plasma osmolality, lithium had a greater effect than sodium on mean arterial pressure, [VP-RNP], [OT-RNP]. For the 20 min infusion of 13% LiCl, there was a significant relationship (P less than 0.033) between delta MAP and log delta[VP-RNP] with a slope of 11.9 mmHg fmol-1 ml-1 (r = 0.5678). Unlike that of Long-Evans rats, infusion of 13% LiCl only did not produce significant changes of mean arterial pressure in Brattleboro rats. For Long-Evans rats, infusion of 0.65% LiCl resulted in more gradual and smaller elevations of blood pressure, [Li+] and smaller decreases in heart rate with no significant changes in plasma osmolality, [Na+], [VP-RNP] and [OT-RNP].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Enhancement of spermidine/spermine N1-acetyltransferase activity by treatment with lithium chloride in Ehrlich ascites tumor cells.

The activity of spermidine/spermine N1-acetyltransferase (SAT) was enhanced in Ehrlich ascites tumor cells by the addition of lithium chloride. Na+ did not affect the enzyme activity. Total RNA was isolated from cells treated with LiCl and the relative abundance of the SAT mRNA was measured by Northern blot analysis. The levels in cells treated with LiCl were comparable to those in control cells. In the treated cells, the biological half-life of SAT was approximately 20 min, which was the same as for control cells. When LiCl and H-7, a protein kinase inhibitor, were added simultaneously to culture, the elevation caused by LiCl of SAT activity was reduced. LiCl did not cause maximum enhancement of the enzyme in cells treated beforehand with a higher concentration of TPA. These results suggest that treatment of Ehrlich ascites tumor cells with LiCl enhanced SAT activity during translation, not during transcription or after translation and that the enhancement of SAT by LiCl is probably mediated by protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗