Short‐term lithium treatment enhances responsiveness of postsynaptic 5‐HT 1A receptors without altering 5‐HT autoreceptor sensitivity: An electrophysiological study in the rat brain

Short‐term lithium administration to rats has previously been shown to enhance 5‐HT neurotransmission through a modification of 5‐HT neuron properties. In the first part of the present study, the effect of lithium on the function of terminal 5‐HT autoreceptors was assessed by comparing in controls and lithium‐treated rats the differential effect of two frequencies of stimulation (0.8 and 5 Hz) and that of methiothepin, a terminal 5‐HT autoreceptor antagonist, on the effectiveness of the electrical activation of the ascending 5‐HT pathway in suppressing dorsal hippocampus pyramidal neuron firing activity. Both procedures produced similar effects in controls and lithium‐treated rats. In the second part of the study, the function of somatodendritic 5‐HT autoreceptors was studied. The effect of intravenous LSD, an agonist of the somatodendritic 5‐HT autoreceptor, on the firing activity of 5‐HT neurons was not modified by the lithium treatment, whereas that of intravenous 8‐OH‐DPAT, a 5‐HT 1A receptor agonist, was increased two‐fold. However, lithium did not alter the responsiveness of 5‐HT neurons to direct microiontophoretic applications of 8‐OH‐DPAT as well as of LSD and 5‐HT. It is concluded that short‐term lithium treatment does not alter the function of terminal and somatodendritic 5‐HT autoreceptors and that it enhances the sensitivity of subset of postsynaptic 5‐HT 1A receptors involved in controlling 5‐HT neuron firing activity, presumably through a feedback loop.