Chronic Fluoxetine Reduces Serotonin Transporter mRNA and 5-HT1B mRNA in a Sequential Manner in the Rat Dorsal Raphe Nucleus
| Autor: | Mark W. Hamblin, Daniel C Root, John F. Neumaier |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Male
Serotonin medicine.medical_specialty Time Factors Nerve Tissue Proteins Serotonergic Rats Sprague-Dawley Dorsal raphe nucleus Fluoxetine Internal medicine medicine Animals RNA Messenger Serotonin Uptake Inhibitors In Situ Hybridization Serotonin transporter 5-HT receptor Serotonin Plasma Membrane Transport Proteins Pharmacology Membrane Glycoproteins biology Chemistry Membrane Transport Proteins Rats Psychiatry and Mental health Endocrinology Receptors Serotonin Receptor Serotonin 5-HT1B biology.protein Raphe Nuclei Antidepressant Carrier Proteins Raphe nuclei Selective Serotonin Reuptake Inhibitors |
| Zdroj: | Neuropsychopharmacology. 15:515-522 |
| ISSN: | 0893-133X |
| Popis: | In major depression in humans and in animal models of depression, there is a defect in serotonergic neurotransmission that can be relieved by chronic antidepressant treatment. One possibility is that this pathologic state is caused by excessive presynaptic autoreceptor activity in serotonergic neurons, and that antidepressants down-regulate the number of these inhibitory receptors, allowing more normal serotonin release to occur. To evaluate this hypothesis, we measured the effects of the antidepressant fluoxetine on neuronal levels of 5-HT 1B receptor mRNA, the putative serotonin terminal autoreceptor in rat brain, and on serotonin transporter mRNA, the direct site of fluoxetine binding. fluoxetine reduced serotonin transporter mRNA briefly, but this was not sustained after 21 days of treatment. However, fluoxetine reduced dorsal raphe 5-HT 1B mRNA levels in a time-dependent and washout-reversible manner. This reduction in 5-HT 1B mRNA was specific to dorsal raphe nucleus and was not found in several postsynaptic (nonserotonergic) regions. These results suggest that chronic fluoxetine may increase serotonin release from axonal terminals by down-regulating the messenger RNA coding for presynaptic 5-HT 1B autoreceptors while causing only transient effects on serotonin transporter mRNA. |
| Databáze: | OpenAIRE |
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