Short-term lithium treatment enhances responsiveness of postsynaptic 5-HT1A 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-HT1A 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 a subset of postsynaptic 5-HT1A receptors involved in controlling 5-HT neuron firing activity, presumably through a feedback loop.
Blier
P
P
Neuroscience Research Center, Faculty of Medicine, University of Montreal, Quebec, Canada.
de Montigny
C
C
Tardif
D
D
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D008094:Lithium / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000502:physiology; D011712:Pyramidal Tracts / Q000502:physiology; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology
D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D008094:Lithium; D000109:Acetylcholine