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

Abstract

Abstract 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.