Long-term 5-HT reuptake blockade, but not monoamine oxidase inhibition, decreases the function of terminal 5-HT autoreceptors: an electrophysiological study in the rat brain.
5-HT-containing terminals possess autoreceptors which modulate the release of 5-HT into the synaptic cleft. Tritiated imipramine ([3H]IMI), and more specifically [3H]citalopram and [3H]paroxetine, bind to a site associated with the 5-HT reuptake carrier on the 5-HT terminals. The function of terminal 5-HT autoreceptors is decreased following long-term treatment with the 5-HT reuptake blocker citalopram. The present study was undertaken to determine whether an increased synaptic availability of 5-HT or, the occupation of the [3H]IMI site, were responsible for this modification. Unitary extracellular recordings were obtained from CA3 dorsal hippocampus pyramidal neurons under chloral hydrate anesthesia in rats treated daily with fluoxetine (10 mg/kg/day X 14 days), a selective 5-HT reuptake blocker, or clorgyline (1 mg/kg/day X 21 days), an inhibitor of type A monoamine oxidase. The function of the terminal 5-HT autoreceptors was assessed by comparing the effectiveness of the electrical stimulation of the ascending 5-HT pathway on the firing activity of hippocampus pyramidal neurons prior to, and following, the administration of methiothepin, an antagonist of the terminal 5-HT autoreceptor, and, by determining the ratio of effectiveness of 0.8 Hz (S1) and 5 Hz (S2) stimulations. Long-term administration of fluoxetine or clorgyline both increased the efficacy of the stimulation of the 5-HT pathway. However, the enhancing effect of methiothepin on the efficacy of the stimulation was attenuated by the fluoxetine, but not by the clorgyline, treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Blier
P
P
Department of Psychiatry, McGill University, Montréal, Québec, Canada.
Chaput
Y
Y
de Montigny
C
C
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003010:Clorgyline / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005473:Fluoxetine; D008719:Methiothepin; D003010:Clorgyline