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

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Abstract

Rats received lithium-containing chow for 48 h. Brain and plasma lithium concentrations ranged from 0.4 to 1.0 mEq/1. 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 the 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.

References (48)

  • R.J. Baldessarini et al.

    Effects of lithium and of pH on synaptosomal metabolism of noradrenaline

    Nature

    (1970)
  • L.J. Birkhimer et al.

    Combined trazodone-lithium therapy for refractory depression

    Am. J. Psychiat.

    (1983)
  • A. Björklund et al.

    5,7-Dihydroxytryptamine: improvement of its selectivity for serotonin neurons in the CNS by pretreatment with desipramine

    J. Neurochem.

    (1975)
  • A. Björklund et al.

    The use of neurotoxic dihydroxytryptamines as tools for morphological studies and localized lesioning of central indoleamine neurons

    Z. Zellforsch.

    (1973)
  • P. Blier et al.

    Electrophysiological investigation on the effect of repeated zimelidine administration on serotonergic neurotransmission in the rat

    J. Neurosci.

    (1983)
  • P. Blier et al.

    Effects of the two antidepressant drugs mianserin and indalpine on the serotonergic system: single-cell studies in the rat

    Psychopharmacology

    (1984)
  • Y. Chaput et al.

    The effects of acute and chronic administration of citalopram on serotonergic neurotransmission: electrophysiological studies in the rat

    Neurosci. Abst.

    (1984)
  • D.S. Charney et al.

    Serotonin function and mechanism of action of antidepressant treatment

    Arch. Gen. Psychiat.

    (1984)
  • R.W. Colburn et al.

    Effect of lithium on the uptake of noradrenaline by synaptosomes

    Nature

    (1967)
  • D.W. Costain et al.

    Enhanced 5-hydroxytryptamine-mediated behavioral responses in rats following repeated electroconvulsive shock: relevance to the mechanism of the antidepressive effect of electroconvulsive therapy

    Psychopharmacology

    (1979)
  • G. Cournoyer et al.

    Lithium addition in tricyclic-resistant unipolar depression: a placebo-controlled study

    Coll. Int. Neuro-Psychopharmacol.

    (1984)
  • C. De Montigny

    Electroconvulsive shock treatments enhance responsiveness of forebrain neurons to serotonin

    J. Pharmacol. Exp. Ther.

    (1984)
  • C. De Montigny et al.

    Tricyclic antidepressants: long-term treatment increases responsivity of rat forebrain neurons to serotonin

    Science

    (1978)
  • C. De Montigny et al.

    Pre- and postsynaptic effects of zimelidine and norzimelidine on the serotonergic system: single-cell studies in the rat

    Acta Psychiat. Scand.

    (1981)
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