Partial 5-HT1A receptor agonist properties of (–)pindolol in combination with citalopram on serotonergic dorsal raphe cell firing in vivo

被引:0
|
作者
Lotta Arborelius
Love Linnér
Carin Wallsten
Sven Ahlenius
Torgny H. Svensson
机构
[1] Department of Clinical Neuroscience,
[2] Magnus Huss M4,undefined
[3] Karolinska Hospital,undefined
[4] 171 76 Stockholm,undefined
[5] Sweden,undefined
[6] Department of Physiology and Pharmacology,undefined
[7] Section of Neuropsychopharmacology,undefined
[8] Karolinska Institutet,undefined
[9] 171 77 Stockholm,undefined
[10] Sweden,undefined
[11] Department of Pharmacology,undefined
[12] Preclinical R&D,undefined
[13] AstraZeneca,undefined
[14] 151 85 Södertälje,undefined
[15] Sweden,undefined
来源
Psychopharmacology | 2000年 / 151卷
关键词
5-HT1A receptor (–)Pindolol Antidepressant activity Electrophysiology Dorsal raphe nucleus Selective serotonin reuptake inhibitor (SSRI);
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摘要
Rationale: Pindolol has been reported to shorten the onset of antidepressant action of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) as well as to increase their efficacy. It has been postulated that pindolol enhances the antidepressant effect of SSRIs by blocking somatodendritic 5-HT1A autoreceptors, thus antagonizing the SSRI-induced feedback inhibition of midbrain 5-HT cell firing. A recent study, however, found that pindolol suppresses the firing rate of central 5-HT cells, suggesting that the compound possesses agonistic activity at 5-HT1A autoreceptors. Objectives: The purpose of the present study was to investigate if acute administration of (–)pindolol antagonizes the decrease in firing rate of dorsal raphe 5-HT cells produced by acute treatment with the SSRI citalopram. Methods: Extracellular recordings of single 5-HT neurons in the dorsal raphe nucleus in anaesthetized rats. Results: Administration of 0.25 or 3.0 mg/kg (IV) (–)pindolol alone decreased the firing rate of a majority of the 5-HT cells studied, an effect that was reversed by the 5-HT1A receptor antagonist WAY100635 (0.1 mg/kg, IV). Neither 0.25 nor 3.0 mg/kg (–)pindolol reversed the citalopram (0.1–0.2 mg/kg, IV)-induced suppression of 5-HT cell activity, but produced a further decrease in firing rate. In contrast, WAY100635 (0.1 mg/kg) completely reversed this effect of citalopram. Yet, pretreatment with 3.0, but not 0.25 mg/kg (–)pindolol significantly attenuated the acute inhibitory effect of citalopram on serotonergic cell firing. Conclusions: The present findings support the previous notion that (–)pindolol possesses prominent agonistic activity at somatodendritic 5-HT1A autoreceptors, but also indicate that it may possess a weak antagonistic action at these receptors.
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页码:77 / 84
页数:7
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