Noradrenergic modulation of central serotonergic neurotransmission: acute and long-term actions of mirtazapine.
Mirtazapine (Org 3770, Remeron) is a new alpha2-adrenoceptor antagonist which is an effective antidepressant drug. An in vivo electrophysiological paradigm in the rat was used to assess the effects of acute and long-term treatment with mirtazapine on pre- and postsynaptic alpha2-adrenoceptors and to determine whether this drug can modulate serotonin (5-HT) neurotransmission. The acute administration of mirtazapine produced a rapid increase in both noradrenaline and 5-HT neurotransmission by blocking both alpha2-adrenergic auto- and heteroreceptors, resulting in an enhanced tonic activation of postsynaptic 5-HT receptors. Long-term administration showed that this tonic activation of postsynaptic 5-HT receptors was most likely enhanced after such a treatment, as a result of a sustained increase in 5-HT neuronal activity in the presence of and due to inactivated alpha2-adrenergic heteroreceptors.
Haddjeri
N
N
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Blier
P
P
de Montigny
C
C
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008134:Long-Term Care; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000078785:Mirtazapine; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000929:Antidepressive Agents, Tricyclic; D011941:Receptors, Adrenergic; D018341:Receptors, Adrenergic, alpha-2; D011985:Receptors, Serotonin; D008803:Mianserin; D012701:Serotonin; D000078785:Mirtazapine; D009638:Norepinephrine