Temporal and regional differences in brain concentrations of lithium in rats

Lithium (Li) concentrations have been estimated in several peripheral tissues (serum, heart, kidney, liver and skeletal muscle) and different brain areas (cortex, caudate nucleus, hypothalamus, diencephalon, midbrain, pons-medulla and cerebellum) at different intervals (0.5 to 48 h) after administrations of 3 mEq/kg of lithium chloride (LiCl). The Li concentrations in the brain areas increased gradually, reaching their peak at 8 h; the hypothalamus showed the highest concentration measured between 0.5 and 8 h; after 8 h the highest concentration was observed in the caudate nucleus, followed approximately by those of the cortex, rest of the diencephalon, and other areas. Concentration of Li in the skeletal muscle, although initially less, was maintained at a higher percentage of the initial level for more than 24 h compared to the other peripheral tissues.     

Distribution of lithium and its effects on electrolyte and norepinephrine metabolism in discrete areas of the rat brain]

Lithium carbonate (Li2CO3) or lithium chloride (LiCl) was administered to rats, and distribution in discrete areas of the brain as well as the effects on electrolytes in the urine, blood and whole brain were investigated. Further, the effects of Li with or without methamphetamine on electrolytes and norepinephrine (NE) metabolism in discrete areas of rat brain were examined. After a single administration of Li2CO3 (2.7 mEq/kg p.o.), the Li concentration in all regions of the brain except the hypothalamus reached the maximum level at 12 hr and decreased gradually. A relatively high concentration was observed in the hypothalamus, a short time after the administration. After repeated administration of Li2Co3 (2.7 mEq/kg/day for 5 or days p.o.), the Li concentration did not increase in any region of the brain in comparison with after a single administration and there were no marked changes in the balance of electrolytes in the plasma and brain despite significant changes in the urinary electrolytes and urine volume. Acute administration of LiCl (2.4 mEq/kg and 1.2 mEq/kgx2 for 2 hr i.p.) did not affect the levels of NE and its metabolites in any region of the brain. Subacute administration of LiCl (2.5mEq/kg X 2/day for 4.5 days i.p.) concomitant with methamphetamine increased the deaminated metabolites of NE in the hypothalamus and hippocampus, whereas no influence was observed on the concentrations of sodium and potassium in any region of the brain. From these results, it is suggested that the hypothalamus is one area where Li exerts its action.     

Cerebral lithium, inositol and inositol monophosphates.

Cerebral regional inositol, inositol-1-phosphate (Ins1P), and inositol-4-phosphate (Ins4P), intermediates in phosphoinositide (PI) cycle, and brain lithium levels were studied in male Han:Wistar rats 24 hr after an intraperitoneal injection of a single dose (2.5-18 mEq./kg) of LiCl. A dose of LiCl higher than 5 mEq/kg caused a remarkable accumulation of Li+ in the brain. Basal brain regional inositol levels (17-22 mmol/kg) were reduced by 6-8 mmol/kg dry brain tissue at doses exceeding 5 mEq/kg of LiCl in all brain regions except the piriform cortex. However, higher doses of LiCl did not cause any further decrease in brain inositol. LiCl increased basal brain regional Ins1P levels (170-240 mumol/kg) by 0.8 mmol/kg dry brain tissue at most, and there were no consistent additional increases of Ins1P at LiCl doses exceeding 5 mEq./kg. Moreover, lithium slightly decreased regional cerebral concentrations of Ins4P. Thus, lithium-induced accumulation of Ins1P or changes of Ins4P levels do not explain lithium-induced decrease in cerebral inositol. Effects of lithium on brain P1 turnover are likely to be multifocal and to differ markedly at different concentrations of Li+ in the brain.     

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)     

Increased sensitivity to serotonergic agonists after repeated electroconvulsive shock in rats

The effect of single and repeated electroconvulsive shock (ECS) (once daily for 7 days) on head twitches produced by 5-HT agonists (LiCl, 5-hydroxytryptophan; 5-HTP and 5-methoxytryptamine; 5-MT) was investigated 1 hr, 24 hr, 5 days and 10 days after the last ECS, while locomotor activity induced by serotonergic agonists (fenfluramine, 3-chlorophenylpiperazine; m-CPP) and antagonists (metergoline, cyproheptadine) was only investigated after 24 hr. 5HT and 5-HIAA concentrations were measured 0.5, 1 and 24 hr after a single ECS and up to 10 days after repeated ECS. Head twitches induced by LiCl were significantly depressed 1 hr after both single and repeated ECS. The number of head twitches produced by LiCl, 5-HTP or 5-MT given 24 hr after single or repeated ECS did not change but it rose significantly 5 and 10 days after the last shock. Repeated ECS increased locomotor activity 24 hr after the last shock. This increase was significantly enhanced by serotonergic antagonists. Biochemical assays showed that a single ECS did not significantly change brain 5-HT and 5-HIAA concentrations 0.5, 1 or 24 hr after the ECS. On the other hand, repeated ECS raised brain 5-HIAA 0.5, 1 and 24 hr or 5 and 10 days and 5-HT 0.5 hr after the final ECS. It is concluded that a single or repeated ECS both depress the serotonergic system response to LiCl but repeated ECS facilitates the response to serotoninomimetics.     

Cerebral Lithium,Inositol and Inositol Monophosphates

Abstract: Cerebral regional inositol, inositol-1-phosphate (InslP), and inositol-4-phosphate (Ins4P), intermediates in phosphoinositide (PI) cycle, and brain lithium levels were studied in male HamWistar rats 24 hr after an intraperitoneal injection of a single dose (2, 5–1. mEq./kg) of LiCl. A dose of LiCl higher than 5 mEq/kg caused a remarkable accumulation of Li⁺ in the brain. Basal brain regional inositol levels (17–2. mmol/kg) were reduced by 6-8 mmol/kg dry brain tissue at doses exceeding 5 mEq/kg of LiCl in all brain regions except the piriform cortex. However, higher doses of LiCl did not cause any further decrease in brain inositol. LiCl increased basal brain regional InslP levels (170–24. μmol/kg) by 0.8 mmol/kg dry brain tissue at most, and there were no consistent additional increases of InslP at LiCl doses exceeding 5 mEq./kg. Moreover, lithium slightly decreased regional cerebral concentrations of Ins4P. Thus, lithium-induced accumulation of InslP or changes of Ins4P levels do not explain lithium-induced decrease in cerebral inositol. Effects of lithium on brain PI turnover are likely to be multifocal and to differ markedly at different concentrations of Li⁺ in the brain.     

Effects of lithium in vitro and ex vivo on components of the adenylate cyclase system in membranes from the cerebral cortex of the rat

The effects of lithium on the activity of adenylate cyclase stimulated by hormones, which act via the stimulatory guanine nucleotide binding subunit (Ns), by forskolin, which acts at the catalytic subunit, and by guanyl-5'-yl imidodiphosphate (GppNHp), which locks the enzyme into a permanently active state, have been compared in a preparation of membranes from the cerebral cortex of the rat. Lithium ions (Li+) in vitro at 2-4 mM inhibited cyclase stimulated by isoproterenol and forskolin, but had no effect on the inhibition induced by met-enkephalin of the enzyme stimulated by forskolin, mediated by the inhibitory guanine nucleotide binding subunit (Ni). Inhibition of the activity stimulated by forskolin and GppNHp was competitive with magnesium (Mg++). In a preparation of slices of cerebral cortex Li+ at 1-2 mM inhibited accumulation of cyclic AMP stimulated by forskolin in a non-competitive manner. In a preparation of membranes from the caudate nucleus, Li+ at 2-4 mM inhibited dopamine-stimulated adenylate cyclase, but this effect was not observed in the presence of additional sodium (Na+). Membranes prepared from animals fed with Li+ to give a mean serum level of 0.52 mM and a mean brain level of 1.32 mM, showed a reduced response to manganese (Mn++), forskolin, isoproterenol and GppNHp in the cerebral cortex, but no change in the degree of activation of the enzyme by either dopamine or forskolin, or the degree of inhibition by met-enkephalin, in the caudate nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of trimethyltin on amino acid concentrations in different regions of the mouse brain

Trimethyltin (TMT) is a neurotoxic compound known to cause marked alterations in brain chemistry. We have previously demonstrated that a single oral dose of TMT produced a dose-dependent decrease in muscarinic cholinergic receptors in mouse brain and significantly elevated glutamine in several regions of the rat brain. This study was designed to determine if TMT produced dose- and time-related alterations in amino acid concentrations in the adult male C57BL/6N mouse brain and in peripheral organs and plasma. In the dose-response study, TMT was administered orally as a single dose of 0, 0.5, 1.0, 3.0 or 5.0 mg/kg and animals were sacrificed 24 hr after treatment. In the time-course study, mice were dosed with TMT at 3.0 mg/kg and sacrificed 4, 12, 24, 48 or 96 hr after dosing. Amino acid concentrations were quantified by HPLC/EC following precolumn derivatization with o-phthalaldehyde-tert-butylthiol. TMT produced dose-dependent increases in aspartate, glutamine and glycine in the caudate nucleus (CN), frontal cortex (FC) and hippocampus (HIP) at 3.0 and 5.0 mg/kg. TMT at 3.0 mg/kg produced significant increases of aspartate in FC and HIP after 48 hr. Glutamine concentrations were significantly increased at 24 and 48 hr in HIP and at 48 hr in CN. Glycine and GABA concentrations were significantly increased at 48 and 96 hr respectively in the HIP. Glutamine was increased in plasma at 4 and 12 hr and in liver at 24 hr. Hyperammonemia occurred in plasma after 8 hr and continued through 24 hr and was accompanied by an increase in serum urea nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lithium modulates striatal reward anticipation and prediction error coding in healthy volunteers

Lithium is one of the most effective mood-stabilizing medications in bipolar disorder. This study was designed to test whether lithium administration may stabilize mood via effects on reward processing. It was hypothesized that lithium administration would modulate reward processing in the striatum and affect both anticipation and outcome computations. Thirty-seven healthy human participants (18 males, 33 with suitable fMRI data) received 11 (±1) days of lithium carbonate or placebo intervention (double-blind), after which they completed the monetary incentive delay task while fMRI data were collected. The monetary incentive delay task is a robust task with excellent test-retest reliability and is well suited to investigate different phases of reward processing within the caudate and nucleus accumbens. To test for correlations with prediction error signals a Rescorla–Wagner reinforcement-learning model was applied. Lithium administration enhanced activity in the caudate during reward anticipation compared to placebo. In contrast, lithium administration reduced caudate and nucleus accumbens activity during reward outcome. This latter effect seems related to learning as reward prediction errors showed a positive correlation with caudate and nucleus accumbens activity during placebo, which was absent after lithium administration. Lithium differentially modulates the anticipation relative to the learning of rewards. This suggests that lithium might reverse dampened reward anticipation while reducing overactive reward updating in patients with bipolar disorder. This specific effect of lithium suggests that a targeted modulation of reward learning may be a viable approach for novel interventions in bipolar disorder.Subject terms: Reward, Bipolar disorder, Motivation     

Multiple-dose sodium polystyrene sulfonate in lithium intoxication: an animal model.

Previous work in our laboratory has demonstrated that sodium polystyrene sulfonate (SPS) significantly lowered serum lithium (Li) concentrations when administered in a single oral dose after an oral dose of lithium in a mouse model. The present study was designed to determine whether: 1) repetitive doses of SPS are effective in lowering serum lithium concentrations, 2) the effect of SPS on lithium concentration is dose related and 3) SPS enhances the elimination of lithium. Mice (N = 144) were given orogastric LiCl (250 mg/kg) and then divided into 4 groups: Controls received water 0, 30, 90, 180, and 360 min. after LiCl; the Full-Dose SPS Group received SPS (5 g/kg/dose) at equivalent times; the Half-Dose SPS Group received SPS (2.5 g/kg/dose) at the same times; and the Elimination Group received water at 0 and 30 min. after LiCl and SPS at 90, 180 and 360 min. after LiCl. Subgroups of each group were sacrificed at 1, 2, 4 and 8 hr post-treatment and serum analyzed for lithium concentrations. Statistical analyses revealed that, when compared to Controls: 1) SPS significantly lowered serum lithium concentrations; 2) this effect was dose-related; 3) repetitive dosing of SPS appears to enhance the elimination of lithium.     

Multiple-Dose Sodium Polystyrene Sulfonate in Lithium Intoxication: An Animal Model

Abstract: Previous work in our laboratory has demonstrated that sodium polystyrene sulfonate (SPS) significantly lowered serum lithium (Li) concentrations when administered in a single oral dose after an oral dose of lithium in a mouse model. The present study was designed to determine whether: 1) repetitive doses of SPS are effective in lowering serum lithium concentrations, 2) the effect of SPS on lithium concentration is dose related and 3) SPS enhances the elimination of lithium. Mice (N=144) were given orogastric LiCl (250 mg/kg) and then divided into 4 groups: Controls received water 0, 30, 90, 180, and 360 min. after LiCl; the Full-Dose SPS Group received SPS (5 g/kg/dose) at equivalent times; the Half-Dose SPS Group received SPS (2.5 g/kg/dose) at the same times; and the Elimination Group received water at 0 and 30 min. after LiCl and SPS at 90, 180 and 360 min. after LiCl. Subgroups of each group were sacrificed at 1, 2, 4 and 8 hr post-treatment and serum analyzed for lithium concentrations. Statistical analyses revealed that, when compared to Controls: 1) SPS significantly lowered serum lithium concentrations; 2) this effect was dose-related; 3) repetitive dosing of SPS appears to enhance the elimination of lithium.     

Effects of lithium chloride on norepinephrine and dopamine metabolism in the rat brain]

Lithium chloride (LiCl) was injected acutely (2.4 mEq/kg and 1.2mEq/kg X 2 for 3 hr, i.p.) or subacutely (2.5 mEq/kg X 2/day for 4.5 days, i.p.) in rats, and behavioral effects, steady state levels of norepinephrine (NE), dopamine (DA) and serotonin (5HT) and the metabolism of intraventricularly administered 14C-NE and 14C-DA in the brain were investigated. Acute and subacute administratin of LiCl suppressed the spontaneous motor activity, but had no effect on the levels of NE, DA and 5HT in the brain. Acute administration of LiCl did not influence the total radioactivity and the levels of NE and its metabolites in NE metabolism, while subacute administration of LiCl increased the deaminated metabolites. In DA metabolism, the deaminated metabolites were decreased by acute administration of LiCl and the O-methylated deaminated metabolites were increased by subacute administration. From these results, it is suggested that LiCl stimulates the monoamine oxidase pathway in NE and DA metabolism and the behavioral sedative effects of LiCl are attributed to the reduced functional activity of brain NE and DA neurons.     

Lithium effects on rat brain glucose metabolism in vivo. Effects after administration of lithium by various routes

The effects of lithium on several brain energy metabolites were investigated in rats. Lithium was administered by three alternative routes: 1) in food, 2) via IP injection, or 3) intracisternally via the suboccipital route. Lithium given in food induced permanent changes, mainly in glycolytic processes and in glycogen content. Lithium injected IP induced, in addition, several changes which depended on the increase in brain lithium concentration following injection of lithium. These changes in brain metabolites disappeared as brain lithium concentration stabilized. Intracisternal injection of lithium produced brain lithium concentrations between 1 and 2 mmoles/kg wet wt., with a mean of about 1.6 mmoles/kg wet wt. Lithium concentrations below about 1.6 mmoles/kg wet wt. induced changes in brain metabolites which were similar to the changes seen after IP injection of lithium. Lithium concentrations above about 1.6 mmoles/kg wet wt. induced changes in several brain metabolites which were at variance with the changes induced by lower lithium concentrations. These changes were in many respects similar to changes in brain metabolites seen in rats exposed to convulsive treatment.It is hypothesized that such metabolic changes during lithium treatment, in discrete areas of the brain with higher concentration of lithium, e.g., hypothalamus, might be related to the prophylactic effect of lithium treatment in man.     

Behavioral depression and its neurochemical correlates at high doses of d-amphetamine in rats

D-Amphetamine at low doses (0.5–1.0 mg/kg; base i.p.) increased spontaneous motor activity (SMA) and induced stereotypy (ST) in rats with the peak effects occurring during the 2nd hr. Dopamine (DA) levels in the caudate nucleus (CN) and diencephalon-midbrain (DM) as well as the noreptnephrtne (NE) level in the DM were markedly elevated at 60 min postdrug. However, at high doses (2 mg/kg or more) the peak effect on SMA occurred during the 1st hr and was decreased, whereas ST was further enhanced; neurochemically, DA level in the DM and serotonin (5-HT) level in the pons-medulla (PM) showed most marked elevation. Decrease in SMA at high doses appears to be partly due to DA-related increase in ST and partly due to an enhanced inhibitory 5-HT mechanism.     

The neurotoxicity of homodimaprit (SKF-91488): Sites of action assessed by the [14C]2-deoxyglucose technique

Homodimaprit (SKF-91488) when injected into the lateral ventricle of the rat resulted in a delayed behavioral syndrome characterized by motor incoordination, hyperexcitability, and aggressive behavior, which occurred 18 hr after injection and ultimately caused death 24–72 hr after injection. In order to determine where the neural effects were occurring, the [¹⁴C]2-deoxyglucose technique was utilized to identify possible sites of brain neural activation. Histological examination revealed that homodimaprit produced periventricular lesions at 18 hr. Autoradiographic analysis demonstrated increased ipsilateral activation in the nucleus accumbens, lateral septal nucleus, bed nucleus of the stria terminalis, caudato-putamen, and the rostral half of the dorsal hippocampus. Bilateral activation was observed in the medial preoptico-hypothalamus, midline thalamic nuclei including the mediodorsal nucleus, and the periventricular central gray. These findings suggest that the delayed behavioral effects of homodimaprit are probably the result of the activation of these specific areas of the brain and the resulting periventricular lesions. The mechanism by which homodimaprit produces these effects, however, remains unknown.     

Alterations in catecholamine levels and turnover in discrete brain areas after food deprivation

The present study determined the levels and turnover of norepinephrine (NE), epinephrine (EPI) and dopamine (DA) in discrete brain areas of rats after 48 hr food deprivation. The steady-state levels of NE, EPI and DA in saline-treated food-deprived rats, relative to satiated rats, remained basically unchanged. However, 48 hr deprivation caused a site-selective potentiation, specifically in the hypothalamic paraventricular nucleus, in the depletion of NE after alpha-methyl-p-tyrosine injection (IP, 200 mg/kg), indicating an increase in NE turnover. While changes in EPI turnover could not be demonstrated, an apparent increase in DA turnover was detected in the perifornical lateral hypothalamus and anterior hypothalamic nucleus after deprivation, while decreased DA turnover was seen in the hypothalamic dorsomedial nucleus and caudate nucleus. These results may reflect specific functions of hypothalamic catecholamines in control of food intake.     

Actions of lithium ions and insulin on glucose utilization, glycogen synthesis and glycogen synthase in the isolated rat diaphragm

The effects of lithium ions and insulin on carbohydrate metabolism of the isolated rat diaphragm were studied and compared. Like insulin, lithium ions caused a conversion of glycogen synthase D to the more active I form of the enzyme. Maximal activation of the enzyme was produced by about 5 mM LiCl. Lithium ions markedly increased glucose utilization and glycogen synthesis by the diaphragm, but the action of this ion appears to be exerted by a mechanism different from that of insulin, since the effects of maximal concentrations of the two agents are additive. In their action on glucose metabolism, lithium ions had a unique ability to direct the glucose taken up by the cell toward glycogen. Insulin and lithium ions had opposite effects on the tissue content of glucose 6-phosphate; insulin increased the tissue level of this metabolite, whereas lithium ions decreased it. ATP and creatine phosphate concentrations were not affected by insulin or lithium ions. The effects of lithium ions on carbohydrate metabolism are exerted at relatively low concentrations of Li, and our results indicate that significant alterations of carbohydrate metabolism may occur when therapeutic or toxic amounts of lithium salts are ingested by man.     

Amphetamine,chlorpromazine and clonidine effects on self-stimulation in caudate or hypothalamus of the squirrel monkey

In 2 separate groups of squirrel monkeys and within 3 animals low rates of intracranial self-stimulation (ICSS) elicited from caudate or lateral hypothalamic brain sites were increased by as much as 200% above control levels by amphetamine (0.5 mg/kg). Thresholds for responding were decreased by 50%. Increasing the drug dose from 2 to 10mg/kg produced response inhibition at both brain sites. The duration of inhibitory action of amphetamine (2.0 mg/kg) on ICSS from the medial forebrain bundle (MFB) area of the lateral hypothalamus was 6 hr. At caudate sites ICSS did not occur until 48 hr had elapsed. A 10 mg/kg dose of amphetamine produced a duration of action of 36 hr in the MFB and 84 hr in the caudate. Chlorpromazine (CPZ) doses of 0.5 and 1.0 mg/kg decreased caudate ICSS significantly more than lateral hypothalamic ICSS. At 1.0 mg/kg the duration of action of CPZ was 6 hr at lateral hypothalamic brain sites and 24 hr at caudate sites. At a 2.0 mg/kg CPZ dose the duration of action was 12 hr in the MFB and 36 hr in the caudate. A dose of 0.10 mg/kg of clonidine blocked high rates of MFB ICSS while within the same animal caudate ICSS was much less affected. Higher doses (0.25 mg/kg) sedated the animal and ICSS was equally inhibited at both sites. These findings, using ICSS as a behavioral measure, suggest that the effects of amphetamine and CPZ involve not only hypothalamic structures but more anterior telencephalic sites as well. The prolonged actions of amphetamine and CPZ on caudate ICSS suggest that drugs acting, in part, on dopamine containing neurons will interfere with certain caudate mediated behavior. Further, since hypothalamic but not caudate ICSS sites are more dose sensitive to drugs that selectively act on NE containing neurons, other amines in addition to NE may play a role in the support of ICSS.     

Monoamine uptake into synaptosomes from various regions of rat brain following lithium administration and withdrawal

The uptake of monoamines into synaptosomes from various regions of rat brain was examined following lithium (Li) treatment (2 mequiv/kg/day) and subsequent withdrawal. In control animals, regional differences were noted in the amount of NA, DA and 5-HT taken up. The consequences of Li administration were found to depend upon the monoamine examined. Dopamine uptake was enhanced, while that of 5-HT was depressed in all regions studied. The effects on NA uptake were seen to be regionally variable, being enhanced in the hypothalamus and striatum and depressed in the midbrain and cortex. Lithium withdrawal resulted in a return towards control values for all regions and substrates except striatum (DA and 5-HT) and midbrain (5-HT), where the uptake remained unaltered or was enhanced with respect to the Li-treated rats. It is suggested that part of the therapeutic effect of Li in mania is due to alterations in the uptake processes for the monoamines, and that the “rebound” mania seen clinically following Li withdrawal may be associated with dopaminergic and tryptaminergic systems, particularly in the striatum and midbrain.     

Central Effects of Lithium in Rats: Lithium Levels,Body Weight and Water Intake

Abstract: Male rats received LiCl for one week either by continuous intracerebroventricular injection from osmotic minipumps or by oral administration in the diet. Control groups received corresponding treatment with NaCl. The intracerebroventricular lithium treatment produced relatively high lithium levels in brain regions (0.6–2.3 mmol/kg) and negligible lithium levels in plasma (less than 0.1 mmol/l) while the oral treatment produced moderate lithium levels in brain regions as well as in blood (0.5–0.9 mmol/kg and 0.5–0.75 mmol/l, respectively). Body weight loss and enhanced water intake occurred in groups given oral lithium treatment as well as in those given lithium via minipumps. The results suggest that administration of lithium by minipumps may be of use to study central actions of lithium.