Short-term lithium administration enhances serotonergic neurotransmission: electrophysiological evidence in the rat CNS.

Rats received lithium-containing chow for 48 h. Brain and plasma lithium concentrations ranged from 0.4 to 1.0 mEq/l. A first series of experiments served to assess the responsiveness of CA3 hippocampal pyramidal neurons to microiontophoretically applied serotonin (5-HT) and norepinephrine (NE). The response of the same neurons to electrical stimulation of the ventro-medial 5-HT pathway was measured after lithium treatment. The responsiveness to 5-HT and NE was not modified whereas the effect of activation of the ascending 5-HT pathway was increased two-fold by the lithium treatment. These neurons were activated to their physiological firing rate by means of small ejection currents of acetylcholine. A pretreatment with the 5-HT neurotoxin 5,7-dihydroxytryptamine abolished the response to the electrical stimulation in lithium-treated rats. In a second series of experiments, unitary recordings of 5-HT neurons were obtained from the dorsal raphe nucleus. The lithium treatment modified neither the number of spontaneously active 5-HT neurons nor their mean firing rate. These results provide direct electrophysiological evidence for the enhancement of 5-HT neurotransmission by short-term lithium treatment through its presynaptic action on 5-HT terminals.