Electrophysiological characterization of the effect of long-term duloxetine administration on the rat serotonergic and noradrenergic systems
| Autor: | L E, Rueter, C, De Montigny, P, Blier |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
Serotonin Plasma Membrane Transport Proteins Serotonin Membrane Glycoproteins Norepinephrine Plasma Membrane Transport Proteins Adrenergic Uptake Inhibitors Symporters Pyridines Membrane Transport Proteins Nerve Tissue Proteins Thiophenes Duloxetine Hydrochloride Hippocampus Clonidine Piperazines Rats Rats Sprague-Dawley Norepinephrine Receptors Serotonin Animals Carrier Proteins Receptors Serotonin 5-HT1 Selective Serotonin Reuptake Inhibitors |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 285(2) |
| ISSN: | 0022-3565 |
| Popis: | Duloxetine is a dual serotonin (5-HT)/norepinephrine (NE) re-uptake blocker with antidepressant potential. In the present in vivo electrophysiological study, the changes in the function of the rat 5-HT and NE systems after 2- and 21-day administration of duloxetine (20 mg/kg/day) were assessed in the dorsal hippocampus and the dorsal raphe nucleus (DRN). The firing rate of DRN neurons was decreased after 2 days of duloxetine, but returned to the control level after 21-day administration. This recovery of firing rate was presumably due to the desensitization of the DRN somatodendritic 5-HT1A autoreceptors found after long-term duloxetine administration. Overall serotonergic tone was assessed by examining the ability of the 5-HT1A antagonist WAY 100635 to alter hippocampal firing. WAY 100635 increased hippocampal firing rates in 21-day treated rats to a greater extent than in 2-day treated or control rats, suggesting that long-term administration induced an increase in endogenous levels of 5-HT in postsynaptic regions. This increase in 5-HT levels was accompanied by selective changes in the 5-HT and NE systems induced by long-term duloxetine administration, i.e., the desensitization of the alpha-2 adrenergic heteroreceptor on 5-HT terminals and the continued blockade of the 5-HT transporters. In contrast, the sensitivity of the alpha-2 adrenergic and terminal 5-HT1B autoreceptors, as well as that of the postsynaptic 5-HT1A receptor after 21-day treatment was unchanged. Therefore, this study demonstrates that duloxetine increases serotonergic tone in a limbic forebrain structure and may therefore be effective in the treatment of depression. |
| Databáze: | OpenAIRE |
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