Long-term antidepressant treatments result
in a tonic activation of forebrain 5-HT1A receptors

by
Haddjeri N, Blier P, de Montigny C
Neurobiological Psychiatry Unit,
McGill University, Montreal,
Quebec, Canada H3A 1A1.
J Neurosci 1998 Dec 1; 18(23):10150-6


ABSTRACT

We report here the first direct functional evidence of an increase in the tonic activation of postsynaptic 5-HT1A receptors by antidepressant treatments. Because 5-HT1A receptor activation hyperpolarizes and inhibits CA3 pyramidal neurons in the dorsal hippocampus, we determined, using in vivo extracellular recording, whether the selective 5-HT1A receptor antagonist WAY 100635 could disinhibit these neurons. Unexpectedly, no disinhibition could be detected in controls. However, after long-term treatment with the tricyclic antidepressant imipramine, the selective 5-HT reuptake inhibitor paroxetine, the reversible monoamine oxidase-A inhibitor befloxatone, the alpha2-adrenergic antagonist mirtazapine, or the 5-HT1A receptor agonist gepirone or multiple electroconvulsive shock (ECS) administration, WAY 100635 markedly increased (60-200%) the firing activity of CA3 pyramidal neurons. Such a disinhibition was absent in rats treated with the nonantidepressant drug chlorpromazine, in rats receiving only one ECS, or in rats receiving multiple ECSs in combination with an intrahippocampal pertussis toxin treatment to inactivate Gi/o-coupled 5-HT1A receptors. These data indicate that such antidepressant treatments, acting on entirely different primary targets, might alleviate depression by enhancing the tonic activation of forebrain postsynaptic 5-HT1A receptors.
5-HT2
5-HT3
5-HT4
5-HT1a
5-HT1b
5-HT1d
5-HT2a
5-HT2c
F11440
MKC-242
Buspirone
Mirtzapine
Flibanserin
Eltoprazine
Aggression
Knockout mice
5-HT2c/5-HT2b
5-HT1a v 5-HT1b
MDMA and 5-HT1a
Suicide and 5-HT1a
5-HT1a and F11440
5-HT1a and anxiety
Anxious 5-HT1a kockout mice
Genomics and mood disorders
5-HT1a agonists as antidepressants
5-HT7 receptor antagonists as antidepressants


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