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PubMed1981

Regulation of lithium in cerebrospinal fluid of the cat by the choroid plexus isolated in situ.

The role of the choroid plexus in regulating the lithium concentration in c.s.f. was studied by the use of the cat choroid plexus isolated in situ in a chamber. LiCl solution (154 mM) was infused i.v. to produce plasma lithium concentrations between 0 and 7.5 m-equiv/l. Over this range of plasma values the c.s.f./plasma ratio remained at 0.58. The plasma and c.s.f. concentrations were constant after about 90 min. Lithium (1.8 or 4.5 m-equiv/l.) was added to the artificial c.s.f. placed in the chamber at the start of a 30-min collection period. The lithium concentration in the chamber fluid was measured at the end of the collection period with the plasma concentration either 0 or greater than that in the chamber. When the lithium gradient was from chamber fluid to blood there was a net loss of lithium from the chamber and the amount was proportional to the gradient. However, when the gradient was in the opposite direction lithium was added to the chamber but the amount added was related to the plasma lithium concentration rather than to the blood-c.s.f. gradient. Altering the potassium concentration in the chamber fluid changed the rate of potassium transport without a comparable effect on lithium movement out of the chamber. Lithium transport by the potassium transport system does not appear to be a major factor in the loss of lithium from the chamber. The data suggest that lithium is transported actively across the choroid plexus into the c.s.f. by the system that is responsible for c.s.f. secretion. Movement from c.s.f. to blood appears to be accomplished primarily by passive diffusion when the c.s.f. concentration significantly exceeds that in the plasma.

Animals↗
PubMedDate not supplied

Suppression of herpes simplex virus infections with oral lithium carbonate--a possible antiviral activity.

In vitro studies have shown an inhibitory effect of lithium salts on herpes simplex virus (HSV) replication by mechanisms that interfere with viral DNA synthesis. Moreover, clinical studies have shown that oral lithium carbonate and topical lithium succinate can suppress genital HSV infections in humans. We conducted a randomized, double-blind, placebo-controlled trial of oral lithium carbonate in 11 healthy subjects age 28-65 years (mean +/- SD age 38 +/- 11 years) who had at least four recurrent HSV infections in the year preceding the study. Six patients completed at least 5 months of lithium therapy at a mean (+/-SD) average daily lithium dose of 437 +/- 185 mg (range, 150-900 mg) and an average serum lithium level of 0.56 +/- 0.20 mmol/L. Overall, lithium treatment resulted in a consistent reduction in the mean number of episodes/month, the average duration of each episode, the total number of infection days/month, and the maximum symptom severity. In contrast, treatment with placebo resulted in an increase in three out of the four severity measures. Although the comparisons between the treatment groups did not achieve statistical significance due to the limited sample size, there was a clear "trend" for a reduction in the total monthly duration of all HSV infections with lithium (p = 0.08). Lithium treatment was well tolerated and produced no deleterious effects on renal or thyroid function. These observations lend support to prior observations of an antiviral activity of lithium, and suggest the possibility that oral lithium may represent a safe prophylactic agent in patients with recurrent HSV infections.

Adult↗
PubMedDate not supplied

[Results of long-term (over 10 years) lithium therapy].

The effectiveness of long term lithium prophylaxis has been studied in thirty patients with bipolar affective disorder. The study covered only these patients receiving prophylactic lithium treatment for at least 10 years, who demonstrated positive response to lithium during the initial five years of the therapy. Standard medical documentation was analyzed for the time-course of the illness within the whole observation period (number, duration and character of remissions) as well as for the history of lithium therapy (serum lithium concentrations, regularity of medical checks, breaks in the lithium treatment). The effectiveness of lithium prophylaxis has been found to diminish with time in as many as 40% of patients subjected to the prolonged lithium therapy, as evidenced by an increased number of recurrences in this group. The explanation for this phenomenon is not clear, particularly that the change in the responsiveness to lithium has been found not to correlate with age, duration of illness, duration of lithium therapy, incidence of somatic diseases and history of lithium treatment (serum lithium concentrations, breaks in the treatment).

Adolescent↗
PubMed1998

The ups and downs of oral lithium dosing.

As a mood-stabilizing agent, lithium has a long history of documented efficacy as well as risks associated with its use. Relative to other psychiatric medications, lithium exhibits a number of unique pharmacokinetic properties. The use of in vivo nuclear magnetic resonance spectroscopy of the 7Li isotope has immense potential to provide an improved understanding of the pharmacokinetic basis of lithium response and nonresponse. The conventional use of orally administered immediate-release preparations of lithium salts in psychiatry is associated with high postabsorptive blood lithium concentrations and trough lithium concentrations in later phases of lithium elimination. These ups and downs of blood lithium concentrations are associated with acute lithium toxicity and symptomatic states, respectively. The use of slow-release lithium formulations represents a long available means of diminishing the postdose variation in serum lithium concentrations. A significant need exists for head-to-head comparisons of the pharmacokinetics and clinical response relationships for slow-release and immediate-release lithium formulations.

Administration, Oral↗
PubMed1988

Lithium increases dynorphin A(1-8) and prodynorphin mRNA levels in the basal ganglia of rats.

The aim of this study was to understand the possible influence of the antimanic drug, lithium, and the neuroleptic, haloperidol, alone or in combination, on the regulation of dynorphin biosynthesis in the striatum. The study was done using male Fisher-344 rats subjected to a regimen of subchronic administration of lithium chloride (4 mEq/kg/day for 1,2,4 or 6 days, i.p.) or a regimen of chronic oral administration of a diet containing lithium carbonate (1.5 g/kg of the diet). Subchronic administration of lithium increased striatal dynorphin A(1-8)-like immunoreactivity (DN-LI) in a time-related fashion. Immunocytochemistry revealed an increase in DN-LI in fibers and cells clustered in 'patches' throughout striatum. The increase in DN-LI was reversible on cessation of lithium administration. Concurrent administration of lithium and an opiate antagonist, naltrexone, or a dopamine receptor antagonist, haloperidol, did not influence the changes induced by lithium. Chronic oral administration of lithium for 21 days led to an increase in DN-LI in the striatum. Co-administration of haloperidol with the 21 day regimen of lithium administration failed to affect the increase in DN-LI. The prodynorphin mRNA abundance in the striatum was quantitated by a molecular hybridization procedure using a prodynorphin 32P-cRNA probe generated from the Riboprobe system. Evidence from the Northern blot analysis reveals that lithium increases the prodynorphin mRNA abundance in the striatum. These results indicate that lithium affects the dynamics of prodynorphin biosynthesis in the striatum, presumably increasing transcription and/or translational processes.

Animals↗
PubMed1991

The mechanisms of action of lithium. I. Effects on serotoninergic and noradrenergic systems in normal subjects.

The effects of 2 weeks of lithium carbonate administration at therapeutic plasma levels were examined in 11 normal volunteers. Serotoninergic function before and after lithium administration was assessed using low-dose intravenous clomipramine hydrochloride challenge, while urinary and plasma metabolites of norepinephrine (NE) were used to assess noradrenergic systems. Long-term lithium administration in normal subjects did not significantly or consistently enhance serotonin-mediated neuroendocrine responses but did increase measures related to neuronal release of NE. No statistically significant effects of lithium on prolactin, corticotropin, or cortisol responses to serotoninergic challenge could be detected. The probability of a type II error was assessed, and a doubling of prolactin level was unlikely to have been missed, although more modest increases (less than 75%) could have been overlooked. After 2 weeks of lithium administration, there were significant increases in 24-hour urinary excretion of NE, normetanephrine, and fractional NE release, compatible with increased neuronal release of NE and a lithium-induced subsensitivity in alpha 2-adrenergic receptor function. These changes were not statistically significant after 1 week of administration, suggesting that increased NE release is characteristic of long- rather than short-term lithium administration. Since previous reports have demonstrated enhanced prolactin responses after short- but not long-term lithium use, the present study points to temporal specificity in lithium's effects on both serotoninergic and noradrenergic function. Lithium's effects on NE release were consistent but small (a 16% increase), while its effects on serotoninergic responses were larger (a 50% increase in prolactin responses) but quite inconsistent, suggesting that neither of these systems is the primary site of action of lithium.

Adrenocorticotropic Hormone↗
PubMed1991

The mechanisms of action of lithium. II. Effects on adenylate cyclase activity and beta-adrenergic receptor binding in normal subjects.

As part of a study of the effects of lithium carbonate on neurochemical function in man, platelet and lymphocyte adenylate cyclase activity and lymphocyte beta-adrenergic receptor binding characteristics were determined before and after 2 weeks of lithium treatment in 10 normal volunteers. Lithium had differential effects on platelet and lymphocyte adenylate cyclase activity. In platelets, basal and stimulated (guanyl imidodiphosphate [Gpp[NH]p] or cesium fluoride) adenylate cyclase activity was significantly augmented by lithium treatment. By contrast, in lymphocytes, Gpp(NH)p- and cesium fluoride-stimulated adenylate cyclase activity was unaffected, while basal activity was decreased modestly after lithium. These results are consistent with preclinical studies that suggest that lithium's effects on adenylate cyclase activity are specific with respect to tissue and brain region and that lithium may interfere with guanine nucleotide binding (G) protein function. Lithium treatment significantly increased the ratio of low- to high-affinity dissociation constants for agonist displacement of antagonist binding to lymphocyte beta-adrenergic receptors (thought to reflect coupling between the beta-adrenergic receptor and stimulatory G protein). Lithium had significant effects on measures associated with signal transduction that might be contrasted to its more subtle effects on neuronal function (norepinephrine release) and neuroendocrine systems (responses to serotoninergic challenge) in these same subjects (reported in a companion article). Lithium's primary site of action may be on signal transduction mechanisms. These effects subsequently may be manifested in changes in neurotransmitter function that may be important to lithium's mood-stabilizing actions.

Adenylyl Cyclases↗
PubMed1984

The effect of lithium carbonate on chemotherapy-induced neutropenia and thrombocytopenia.

Lithium carbonate ameliorates neutropenia associated with cancer chemotherapy. The effect of lithium on platelet suppression has not, however, been well established. In the present study, five patients with ovarian carcinoma received daily lithium during alternate cycles of treatment with hexamethylmelamine, cyclophosphamide, adriamycin, and cis-platinum. Analysis of myelosuppression was performed on 24 paired consecutive cycles given at identical doses, one with and one without lithium. During lithium cycles, nadir leukocyte, neutrophil, and platelet counts were significantly higher (P less than 0.01, less than 0.01, less than 0.05 respectively) and the interval between treatments was shorter (P less than 0.01). One patient who has received 11 cycles of chemotherapy continues to receive 100% doses owing to the beneficial effect of lithium on chemotherapy-induced thrombocytopenia. Lithium was poorly tolerated by some patients because of either tremor or nausea and vomiting, in spite of nontoxic serum lithium levels. The amelioration of drug-induced platelet suppression as well as neutrophil suppression noted in this study suggests that lithium's effect on hematopoiesis is not limited to stimulation of neutrophil production. The ability of lithium to decrease chemotherapy-induced myelosuppression suggests that lithium administration may facilitate escalation of chemotherapy doses in selected patients.

Agranulocytosis↗
PubMed1986

Acute inhalation toxicopathology of lithium combustion aerosols in rats.

Male and female F344/Lov rats were exposed to aerosols produced by burning lithium metal under conditions designed to stimulate a fire in the containment building of a fusion reactor. Lithium combustion aerosols were generated by sweeping lithium vapor into air atmospheres with controlled CO2 and H2O concentrations. Chemical analyses of the aerosols produced indicated a dependence of the chemical form of carbon dioxide concentrations and relative humidity. Under conditions of low CO2 concentration and low relative humidity (less than 25%), the aerosol was predominantly lithium monoxide with some lithium hydroxide and about 12% lithium carbonate. Under conditions of high relative humidity (greater than 75%), the aerosol was primarily lithium hydroxide with about 23% lithium carbonate. Although these two aerosols might be expected to have different acute toxicities based on their differing alkalinities, the 14-day LC50 values (with 95% confidence limits) determined after 4-hr exposures were 940 (730-1200) mg/m3 for the lithium oxide and hydroxide mixture and 960 (830-1200) mg/m3 for the lithium hydroxide aerosols. Histopathologic lesions were observed in the nasal turbinates, larynx, and occasionally in the lungs with both aerosols. The most prominent lesions were necrotizing laryngitis and ulcerative rhinitis. Pulmonary lesions represented a secondary extension of the upper respiratory tract lesions rather than a primary manifestation of lithium toxicity. The similarities in the LC50 values and also in the histopathologic lesions observed suggest that any Li2O in the aerosol reacted rapidly with water vapor in the respiratory tract to form LiOH prior to deposition.

Aerosols↗
PubMed2001

Gametogenic responses of the testis in spotted munia (Lonchura punctulata; Aves) to oral administration of lithium chloride.

In the present study, the effects of orally-administered lithium on testicular morphology were examined in the spotted munia (Lonchura punctulata), a seasonally breeding sub-tropical finch. Adult males were procured from natural populations during the month of August, a time when these birds begin to show seasonal reproductive maturity in an annual cycle. Both during the period of acclimation, and throughout the subsequent experimental period, the birds were maintained in an open aviary simulating natural environmental conditions. Lithium was dissolved in distilled water and was administered via the oral route by means of a commercially available stomach-tube. A total of five experimental groups were utilized. The first group (Group A) served as control and received lithium-free distilled water in a similar manner. In the remaining four groups, lithium was administered daily as follows: Group B (2.5 mEq/Kg body weight for 5 days); Group C (2.5 mEq/Kg for 10 days); Group D (5.0 mEq/Kg for 5 days) and Group E (5.0 mEq/Kg for 10 days). All lithium administrations were carried out between 14:00 and 15:00h. Twenty-four hours after the last oral lithium, final body weights were recorded, blood samples were obtained (by brachial vein puncture for the measurement of serum lithium) and the animals were sacrificed, and testes were collected for histological studies. Our results indicated that lithium treatment led to a significant reduction in testicular weight and seminiferous tubular diameter, and a marked degenerative changes in germ cells in that most of the spermatids and mature spermatozoa showed necrotic changes and were sloughed off from the seminiferous tubular epithelium. Complete desquamation and loss of germ cells, and their clump formation were also noted within many seminiferous tubular lumen. Notably these adverse effects were observed when serum lithium levels were within the therapeutic range for human. These results confirm our earlier report on lithium's adverse effects on testicular function, and extend further to show that lithium indeed has a significant adverse effect on the histomorphology, and, thus, the function of the testis in birds.

Animals↗
PubMed1983

Indomethacin but not aspirin increases plasma lithium ion levels.

The pharmacokinetic drug interactions between lithium sulfate and the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin and aspirin were studied in ten normal female volunteers restricted to 150-mEq/day of sodium. Indomethacin decreased renal lithium ion elimination by 23% and caused a 40% increase in steady state plasma lithium ion levels. In contrast, aspirin had no effect on plasma lithium ion levels and increased renal lithium ion elimination by only 6%. Renal prostaglandin E2 excretion was suppressed by 50% to 60% of control levels by indomethacin and by 65% to 70% by aspirin. A clinically important drug interaction with the risk of lithium intoxication can occur between lithium salts and indomethacin. However, aspirin did not affect steady state plasma levels of lithium ion and thus may be preferable for antirheumatic treatment of patients undergoing long-term therapy with lithium salts. Frequent monitoring of plasma lithium ion levels is absolutely necessary in patients receiving both lithium salts and NSAIDs.

Adult↗
PubMed2002

Long-term lithium treatment prevents neurotoxic effects of beta-bungarotoxin in primary cultured neurons.

Lithium is the most commonly used drug for the treatment of manic-depressive illness. The precise mechanisms underlying its clinical efficacy remain unknown. In this study, we found that long-term exposure to lithium chloride protected cultured cerebellar granule neurons (CGNs) against beta-bungarotoxin (beta-BuTX)-induced neurotoxicity. This neuroprotection was exhibited at the therapeutically relevant concentration of 1.2 mM lithium. Pretreatments for 3-5 days (long-term) were required for protection to occur; but a 3 hr treatment (short-term) was ineffective. In contrast, a longer treatment for 6-7 days or a higher concentration of 3 mM lithium led not only to loss of the neuroprotective effect but also to a neurotoxic effect. These findings suggest that lithium protection is limited to its narrow window of concentration and apparently relevant to its narrow therapeutic index in clinical application. Measurement of intracellular calcium [Ca(2+)](i) revealed that neurotoxic concentrations of beta-BuTX markedly increased [Ca(2+)](i), which could be attenuated by long-term, but not short-term, lithium treatment. Thus, the protection induced by lithium in CGNs was attributed to its inhibition of calcium overload. In addition, the Ca(2+) signaling pathway, including reactive oxygen species production and mitochondrial membrane potential reduction, along with the neurotoxic effect of beta-BuTX was blocked by long-term, but not short-term, lithium treatment. All of these results indicate that a crucial step for lithium protection is modulation of [Ca(2+)](i) homeostasis and that lithium neurotoxicity possibly, at least in part, is due to calcium overload. In conclusion, our results suggest that lithium, in addition to its use in treatment of bipolar depressive illness, may have an expanded use in intervention for neurotoxicity.

Analysis of Variance↗
PubMed1983

'Insulin-like' effects of lithium ion on isolated rat adipocytes. II. Specific activation of glycogen synthase.

Lithium ion, like insulin, activated adipocyte glycogen synthase with or without glucose in the medium. However, the effect of lithium ion was much greater than that of insulin under both conditions. The lithium-activated glycogen synthase was stable to both Sephadex chromatography and ethanol precipitation of the enzyme, indicating that the effect of lithium ion on glycogen synthase was through covalent modification of the enzyme. Glycogen synthase was significantly activated by lithium ion under conditions where concentrations of cellular ATP were unaffected. The effect of lithium ion on glycogen synthase was rapid and observed at concentrations as low as 1 to 3 mM, reaching a maximum at the concentration of 40 mM. It was thus the most sensitive of all the effects studied (see previous paper). Insulin further stimulated glycogen synthase at low concentrations but not at maximal concentration of lithium ion. Lithium-activated glycogen synthase was inhibited by both epinephrine and dibutyryl cyclic AMP, but was not affected by the removal of extracellular Ca++. Interestingly, lithium ion had no detectable effect on basal pyruvate dehydrogenase as well as on epinephrine-stimulated phosphorylase. The failure of lithium ion to thus mimic insulin actions on pyruvate dehydrogenase and on phosphorylase suggests that the action of lithium ion on glycogen synthase is quite specific and may be mediated by stimulating a phosphatase or by inhibiting a protein kinase acting specifically on glycogen synthase.

Adipose Tissue↗
PubMed1979

A micropuncture study of the renal handling of lithium.

Although clearance studies in man and experimental animals indicate that filtered lithium is reabsorbed primarily in the proximal tubule, it is unclear whether lithium is also reabsorbed in distal portions of the nephron. Micropuncture studies were, therefore, performed to determine the nephron sites involved in lithium transport during free flow. A method was established to estimate the concentration of lithium in nanoliter samples, using the Helium Glow photometer, which permitted the accurate measurement of lithium in tubular fluid samples over a range from 0.5--30.0 mM. Approximately 56% of filtered lithium and tubular fluid was reabsorbed at the end of the proximal convolution, while at the early distal tubule 75% of filtered lithium and water was reabsorbed. There was no change in net transepithelial movement of lithium beyond the loop of Henle. These data suggest that lithium transport is localized to the proximal tubule, including the pars recta. Lithium reabsorption does not occur in distal tubule or collecting duct. Beyond the early distal tubule net movement of lithium and sodium is dissociated.

Animals↗
PubMed2006

Lithium and inositol: effects on brain water homeostasis in the rat.

RATIONALE: Since its earliest use in psychiatry, lithium has been known to alter body water homeostasis. Although lithium is also known to decrease the concentration of inositol, an important brain osmolyte, little is known of the effects of lithium on brain water homeostasis. OBJECTIVE: To determine whether lithium alters brain water homeostasis, and, if so, whether the mechanism involves changes in inositol concentration. MATERIALS AND METHODS: Rats were fed regular food or regular food plus lithium chloride for either 11 days or 5 weeks. Brains were dissected and assayed for tissue water by the wet-dry method and for inositol by gas chromatography-mass spectrometry. RESULTS: We found a statistically significant (p=0.05, corrected) 3.1% mean elevation in frontal cortex tissue water in 5-week lithium-fed rats (86.7+/-3.9%), compared to control rats (83.6+/-2.6%). Inositol concentration correlated inversely with percent tissue water (r=-0.50, p=0.003, corrected) in pooled samples of 5-week lithium-fed rats, and was significantly lower in frontal cortex and hippocampus of 5-week lithium-fed rats, compared to controls. Rats fed lithium for 11 days did not differ significantly from controls on either variable. CONCLUSIONS: This is the first report of a lithium-induced increase in brain tissue water. Although the mechanism is unclear, it does not appear to result from changes in brain inositol concentration or blood sodium concentration. This finding may have implications for the therapeutic or toxic effects of lithium on brain, because increased tissue water can augment cell excitability.

Animals↗
PubMed1989

Effects of lithium ex vivo on the GTP-mediated inhibition of calcium-stimulated adenylate cyclase activity in rat brain.

The aim of this study was to investigate the effects of chronic lithium treatment on calcium (Ca2+)-stimulated adenylate cyclase activity in rat striatum and hippocampus, and to elucidate the effect of lithium treatment on the neurotransmitter/GTP-mediated inhibition of Ca2+-stimulated enzyme activity in the two brain areas. Lithium treatment, which gave a serum-lithium concentration of 0.9 +/- 0.16 mmol/l, enhanced Ca2+-stimulated enzyme activity in the hippocampus but reduced this activity in the striatum. Serotonin (5-HT) dose dependently reduced Ca2+-stimulated adenylate cyclase activity in the hippocampus, and chronic lithium administration reduced the ability of 1 microM 5-HT to inhibit Ca2+-stimulated enzyme activity. Furthermore, the 5-HT-induced GTP-mediated inhibition of Ca2+-stimulated adenylate cyclase activity in the hippocampus was markedly decreased by lithium. Increasing concentrations of dopamine in the striatum did not, however, affect Ca2+-stimulated adenylate cyclase activity and the inhibition of enzyme activity observed with increasing concentrations of GTP was not influenced by chronic lithium treatment. These results demonstrate that lithium ex vivo exerts dual and region-specific effects on Ca2+-stimulated adenylate cyclase in the brain. Furthermore, long-term administration of lithium could reduce the inhibitory effect of 5-HT on adenylate cyclase in the hippocampus, by influencing the inhibitory GTP-binding protein. The effects of lithium on serotonergic and dopaminergic neurotransmission could be involved in the therapeutic actions of lithium in manic-depressive illness.

Adenylyl Cyclases↗
PubMed1992

The effects of lithium isotopes on the myo-inositol 1-phosphatase reaction in rat brain, liver, and testes.

Enzyme inhibition studies were performed with several lithium isotopes in order to more precisely define how lithium inhibits the enzyme myo-inositol 1-phosphatase. This lithium-induced inhibition is thought to be central to the therapeutic effects of lithium in the treatment of manic-depressive disorder. Naturally occurring lithium (NLi) exists as a combination of isotopes: 6Li and 7Li. Lethality studies were performed comparing 6LiCl, 7LiCl, and NLiCl, did not demonstrate a differential effect as previous studies had suggested. Enzyme inhibition studies were performed with these individual lithium isotopes, and compared to the effects of the naturally occurring combination (NLi) on the inhibition of myo-inositol 1-phosphatase using a partially purified enzyme preparation from rat brain, liver and testes. Identical inhibition was observed with all lithium isotopes and their combinations. In addition, both D- and L-myo-inositol 1-phosphates were used as enzyme substrates and found to be equivalent. These experiments, along with previous work demonstrating lithium acting as an uncompetitive inhibitor in the reaction, and the lack of lithium binding sites on the enzyme, suggests the hypothesis that lithium is possibly inhibiting this reaction by interfering with the formation of a transition cyclic intermediate, myo-inositol 1,3-cyclic phosphate, which may be formed from either the D- or L-substrates. This proposal is in contrast to previous suggestions regarding the inhibitory mechanism of action of lithium on the myo-inositol 1-phosphatase reaction.

Analysis of Variance↗
PubMed1986

Conditioned taste aversions and changes in motor activity in lithium-treated rats. Mediating role of the area postrema.

The role of the area postrema in mediating taste aversions conditioned with the administration of lithium was examined in experiment 1. Rats with lesions of the area postrema or with sham lesions were given pairings of a novel taste with either intraperitoneally or intragastrically administered lithium chloride (LiCl; 10 mg/kg of a 0.15 M solution of lithium chloride) or a similar concentration of NaCl (control groups). Sham-lesioned rats exhibited strong taste aversions when lithium was used for the conditioning procedure and given intraperitoneally or intragastrically (P less than 0.01). Rats with lesions of the area postrema failed to develop taste aversions after the administration of lithium by either route. In experiment 2, rats with lesions of the area postrema and rats with sham lesions were given 30 min access to a 0.12 M solution of NaCl and 2 days later to a 0.12 M solution of lithium. The sham-lesioned animals drank less lithium than NaCl (P less than 0.02) and exhibited depressions in levels of activity following the ingestion of lithium. Rats with lesions of the area postrema drank more lithium than the sham-lesioned rats (P less than 0.01) and did not show behavioral depression after the ingestion of lithium. These data suggest that in the absence of the chemically-sensitive area postrema intragastrically administered lithium does not produce conditioned taste aversions or depression of activity in rats.

Animals↗