Search

Rats were treated with lithium administered either via the food or by intraperitoneal injection. Lithium administration via the food results in a rather stable serum lithium concentration, whereas lithium injection results in a varying serum lithium concentration whereby a sharp increase shortly after the injection is followed by an exponential decline until the next injection (Plenge et al. 1981) After 5 months of lithium treatment the 5HT transport protein, the β-adrenergic receptor and several other brain proteins were determined. The 5HT transport protein, labelled with [H]paroxetine, was found to be decreased in the lithium-injected rats (B=347 fmol/mg protein) but was unchanged in the lithium-fed rats (B=389 fmol/mg protein), as compared with control rats (B=396 fmol/mg protein), and therefore probably is a specific effect only seen with varying lithium concentration. In contrast, the neuronal membrane marker protein D3 was decreased in the lithium-fed rats (88% of the control value), and showed a trend towards decrease in the lithium-injected rats. The decrease in D3 in the lithium-fed rats may indicate some neuronal damage due to the continous presence of lithium. This damage may be more pronounced than in rats, where periods of low lithium concentration enable repair to take place. The β-adrenergic receptor and the neural cell adhesion molecule NCAM were unaffected by the different lithium treatment regimens. Lithium has been reported to inhibit the 5HT1B receptor (the serotonin autoreceptor). We postulate that the two effects, i.e. overall lithium-induced inhibition of the 5HT autoreceptor and the down-regulation of the 5HT transport protein in rats with changing lithium concentration shown in the present study, may combine to augment the 5HT concentration in the synaptic cleft; increased 5HT in the cleft possibly being relevant in prophylactic lithium treatment of manic depressive disorders. [ABSTRACT FROM AUTHOR]

Striatal dopamine and its metabolites were studied in rats given lithium chloride in the diet. Results showed an increase in homovanillic acid and 3,4-dihydroxyphenylacetic acid levels but no significant change in dopamine concentration after 3 weeks of lithium administration. There was no change in tyrosine hydroxylase activity after 1, 2, and 3 weeks treatment. The results indicate an increase in the release and turnover of dopamine in the lithium-treated animals. [ABSTRACT FROM AUTHOR]

Lithium chloride was administered chronically in two dose levels to rats giving serum lithium concentrations of about 0.4 and 0.7 meq/l. Treatment with the lower lithium dose did not affect monoamine metabolism in the brain. With the higher dose, accumulation of labelled 5-HT and 5-HIAA in the brain during intravenous infusion of H-tryptophan was increased. The effect was also present in the spinal cord following transection of 5-HT neurons, thus occurring independently of nerve impulse activity. The disappearance of labelled 5-HT from brain after intravenous injection of H-tryptophan was reduced in lithium-treated animals, indicating that lithium diminishes release of 5-HT from its storage sites. Brain tryptophan was augmented by lithium, whereas levels of free and total tryptophan in serum as well as its catabolism, reflected by liver tryptophan pyrrolase activity, were unaltered. Accumulation and disappearance of labelled dopamine and noradrenaline formed from C-tyrosine in brain were not changed by lithium treatment. It is concluded that chronic treatment of rats with lithium within the low dose range recommended for man affects 5-HT, but not catecholamine synthesis and turnover in brain. [ABSTRACT FROM AUTHOR]

Patients given long-term treatment with lithium often develop an impairment of renal water reabsorption which may lead to clinically significant adverse reactions. A convenient measure of this impairment may be obtained using the ratio of urine volume (V) divided by lithium clearance (C). When data from a large group of patients were recalculated, this ratio showed a statistically significant correlation with the serum lithium level. This finding supports the suggestion that patients might advantageously be maintained at lower serum levels than those commonly employed. [ABSTRACT FROM AUTHOR]