التفاصيل البيبلوغرافية
| العنوان: |
Early desensitization of somato-dendritic 5-HT autoreceptors in rats treated with fluoxetine or paroxetine. |
| المؤلفون: |
Poul, Emmanuel, Laaris, Nora, Doucet, Edith, Laporte, Anne-Marie, Hamon, Michel, Lanfumey, Laurence |
| المصدر: |
Naunyn-Schmiedeberg's Archives of Pharmacology; 1995, Vol. 352 Issue 2, p141-148, 8p |
| مستخلص: |
Electrophysiological and autoradiographic approaches were used to assess possible changes in 5-hydroxytryptamine (serotonin) 5-HT receptors in the rat dorsal raphe nucleus after a subchronic treatment with fluoxetine or paroxetine, two specific serotonin reuptake inhibitors with antidepressant properties. Fluoxetine or paroxetine were injected daily (5 mg/kg, i.p.) for various time periods up to 21 days. Electrophysiological recordings performed 24 h after the last injection showed that the potency of the 5HT receptor agonist, 8-OH-DPAT, to depress the firing of serotoninergic neurons in the dorsal raphe nucleus within brain stem slices was significantly reduced as early as after a 3-day treatment with either drug. The proportion of recorded neurons showing desensitization of somatodendritic 5-HT autoreceptors increased along the treatment from ∼40% on the 3rd day to 60-80% on the 21st day. At no time during the treatment, was the specific binding of [H]8-OHDPAT (agonist radioligand) or [H] WAY-100 635 (antagonist radioligand) to 5-HT receptors modified in the dorsal raphe nucleus or in other brain areas, suggesting that neither the density nor the coupling of these receptors to G-proteins were probably altered in rats injected with fluoxetine or paroxetine for up to 21 days. These results show that adaptive desensitization of somatodendritic 5-HT autoreceptors within the dorsal raphe nucleus can already be detected after a 3-day treatment with selective serotonin reuptake inhibitors. Rather than the desensitization per se, it may be the progressive increase in the number of serotoninergic neurons with desensitized 5-HT autoreceptors which plays a critical role in the (slowly developing) antidepressant action of these drugs. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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