Effects of short-term lithium administration on tryptophan levels and 5-hydroxytryptamine synthesis in whole brain and brain regions in rats

Berggren, Ulf

doi:10.1007/bf01244102

Cited by 11 publications

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“…Swann et al [16], Berggren [2] and Herrero et al [8] have shown that lithium increases the transport of tryptophan into the brain, thereby increasing its concentration in the serotoninergic endings and inducing the synthesis of serotonin released into the synaptic cleft.…”

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

“…This effect is thought to be brought about by lithium bringing about an increase in the tryptophane uptake inside the brain and inducing an increase in serotonin synthesis within the brain's neurons [2,8].Many authors have noted that the behavioural syndrome in rats and mice deemed 'head twitching' is induced by the administration of serotonin precursors (5-hydroxytryptophan) or serotonin agonists (e.g. DOI), and have utilized this effect as a model for response as mediated by 5-HT2 The effectiveness of lithium in the treatment of affective disorders is well documented.…”

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The effect of short-term lithium treatment on head twitches induced by 5-hydroxytryptophan in mice

Szymczyk

Danilczuk

Wielosz

2015

Current Issues in Pharmacy and Medical Sciences

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Researchers have demonstrated that lithium potentiated the 5-hydroxytryptophan induction of head twitches in rats that was abolished by pretreatment with the serotonin synthesis inhibitor -p-chlorphenylalanine [15]. This effect is thought to be brought about by lithium bringing about an increase in the tryptophane uptake inside the brain and inducing an increase in serotonin synthesis within the brain's neurons [2,8].Many authors have noted that the behavioural syndrome in rats and mice deemed 'head twitching' is induced by the administration of serotonin precursors (5-hydroxytryptophan) or serotonin agonists (e.g. DOI), and have utilized this effect as a model for response as mediated by 5-HT2 The effectiveness of lithium in the treatment of affective disorders is well documented. However, the mechanism of this effect is still unknown. The purpose of this study was to investigate the effect of lithium on serotonergic neurons. The evaluation of the serotoninergic system activity was performed on the basis of an experimental model of head twitch response triggered by direct or indirect stimulation of serotonin 5-HT2 receptors in the brain. The obtained results indicated that the lithium chloride co-applied with a direct precursor of serotonin -5-hydroxytryptophan used in a threshold dose and with carbidopa, generated head twitch response in mice. What is more, an enhancement of head twitch response in mice was observed after repeated 5-hydroxytryptophan application in head twitch-evoking doses. Moreover, inhibition of the serotonine storage in nerve endings in mice was evoked by reserpine administration. Furthermore, lithium increased the effect of 5-hydroxytryptophan given in a threshold dose and a head twitchevoking dose, respectively. In addition, when P-chlorphenylalanine (pCPA), an inhibitor of the serotonin synthesis within the serotonergic neurons, was given simultaneously with the lithium chloride, carbidopa and 5-hydroxytryptophan in the threshold dose, as well as with the lithium chloride and 5-hydroxytryptophan given at head twitchevoking dosage, pCPA administration decreased the number of head twitches responses in both experimental models, as well as in the reserpinized mice subjected to the lithium chloride and 5-hydroxytryptophan application. Finally, 5,7-dihydroxytryptamineevoked serotoninergic nerve endings destruction led to absolute inhibition of headtwitch response when observed after the lithium and 5-hydroxytryptophan application. Moreover, the increase by lithium 5-hydroxytryptophan-evoke head twitch response was inhibited by administration of the ritanserine -a 5-HT2 serotonin receptor blocking agent. In summary, our data show that lithium induced an enhancement of serotonergic neurotransmission due to its action on presynaptic serotonergic terminals.

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Section: Discussionmentioning

confidence: 99%

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