"Antidotal Thirst": A Response to Intoxication

Smith, Donald F.; Balagura, Saul; Lubran, M.

doi:10.1126/science.167.3916.297

Cited by 33 publications

(13 citation statements)

References 6 publications

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“…It was recently suggested that lithium polyuria in the rat resulted from excessive intake of water (34). The present experiments exclude this explanation.…”

supporting

confidence: 49%

On the Mechanism of Lithium-Induced Diabetes Insipidus in Man and the Rat

Forrest¹,

Cohen²,

Torretti³

et al. 1974

J. Clin. Invest.

274

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A B S.T R A C T The mechanism of lithium-induced diabetes insipidus was investigated in 96 patients and in a rat model. Polydipsia was reported by 40% and polyuria (more than 3 liter/day) by 12% of patients receiving lithium. Maximum concentrating ability after dehydration and vasopressin was markedly impaired in 10 polyuric patients and was reduced in 7 of 10 nonpolyuric patients studied before and during lithium therapy. Severe polyuria (more than 6 liter/day) was unresponsive to trials of vasopressin and chlorpropamide, but improved on chlorothiazide. Rats receiving lithium (3-4 meq/kg/day) developed massive polyuria that was resistant to vasopressin, in comparison to rats with comparable polyuria induced by drinking glucose. Analysis of renal tissue in rats with lithium polyuria showed progressive increase in the concentration of lithium from cortex to papilla with a 2.9-fold corticopapillary gradient for lithium. The normal corticopapillary gradient for sodium was not reduced by lithium treatment. The polyuria was not interrupted by brief intravenous doses of vasopressin (5-10 mU/kg) or dibutyryl cyclic AMP (10-15 mg/kg) capable of reversing water diuresis in normal and hypothalamic diabetes insipidus rats (Brattleboro strain). The present studies suggest that nephrogenic diabetes insipidus is a common finding after lithium treatment and results

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“…It was recently suggested that lithium polyuria in the rat resulted from excessive intake of water (34). The present experiments exclude this explanation.…”

supporting

confidence: 49%

On the Mechanism of Lithium-Induced Diabetes Insipidus in Man and the Rat

Forrest¹,

Cohen²,

Torretti³

et al. 1974

J. Clin. Invest.

274

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“…Rather, Li may act directly upon thirst mechanisms (Smith & Balagura, 1972), so that the polyuria is secondary (Smith, Balagura & Lubrau, 1970). Thus in the DI rat, Li produces a primary polydipsia, while in LE rats polyuria may be induced perhaps in combination with a central neural action on water intake.…”

Section: Discussionmentioning

confidence: 99%

Time Course of Lithium‐induced Alterations in Renal and Endocrine Function in Normal and Brattleboro Rats With Hypothalamic Diabetes Insipidus

Balment

Jones

Henderson

1977

British J Pharmacology

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I A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin. 2 During the first 24 h, Li-supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li-supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities. 3 The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li-supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually reestablished, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement. 4 Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li-supplement. 5 Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period. 6 Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals was increased. 7 It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.

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“…Lithium causes polydipsia which may act to increase renal activity and thus lithium excretion (Smith et al, 1970). Alternatively, when water was not present the rats learned to avoid both bottles, whereas when water was available in one bottle this increased the probability of sampling the wrong bottle (i.e., lithium) since these were switched over each day.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have used either water (Smith et al, 1970) or saline (Thomsen et al, 1974) for the investigation of lithium toxicity. The present work supports the view that both liquids act, presumably, to reduce the retention of lithium ions.…”

Section: Discussionmentioning

confidence: 99%

“…The causal sequence of these symptoms, however, is unclear although their similarity to those of diabetes insipidus has been attributed to the reversible inhibition of anti-diuretic hormone in the rat kidney (Harris & Jenner, 1968). Smith, Balagura & Lubran (1970) suggest that rats exhibit 'antidotal thirst' for water which acts, through the renal system, to rid the body of toxic lithium ions. Evidence has since emerged to show that high doses of lithium can impair conservation of sodium, so that rats administered lithium in food choose to drink saline rather than water, thus minimizing lithium toxicity (Schreiber & Roh&ovi, 1971;Thomsen, Jensen & Olesen, 1974).…”

Section: Introductionmentioning

confidence: 99%

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Voluntary Lithium Intake, ‘Antidotal Thirst’ and Concurrent Behaviour of Rats

Langham¹,

Syme

1975

British J Pharmacology

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I Voluntary intake of various pair combinations of fluids (100 mM, 10 mM LiCl, 10 mM NaCl, water) and body weight was measured daily in rats. 2 More lithium was consumed when water was available. 3 When offered a lithium-sodium choice the rats did not consume significantly more saline than water on the previous trial. While saline consumption increased over the two days, lithium decreased slightly. 4 Following the lithium-only trial, water and saline were provided. Marked polydipsia was observed on the first day and the rats drank more water than saline. On the second day there was a significant drop in saline intake while water consumption returned to baseline levels. 5Behavioural measurements overall confirmed the depressant effect of lithium: decreased ambulation and rearing and increased time spent immobile/grooming. 6 These findings are discussed with reference to lithium toxicity, which may be a confounding variable in studies concerned with the effects of this salt on the behaviour of laboratory rodents. Behavioural irritability such as aggression reported in situations using long-term lithium treatment may be reduced by provision for voluntary saline consumption.

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"Antidotal Thirst": A Response to Intoxication

Cited by 33 publications

References 6 publications

On the Mechanism of Lithium-Induced Diabetes Insipidus in Man and the Rat

On the Mechanism of Lithium-Induced Diabetes Insipidus in Man and the Rat

Time Course of Lithium‐induced Alterations in Renal and Endocrine Function in Normal and Brattleboro Rats With Hypothalamic Diabetes Insipidus

Voluntary Lithium Intake, ‘Antidotal Thirst’ and Concurrent Behaviour of Rats

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