Autoreceptors remain functional after prolonged treatment with a serotonin reuptake inhibitor

Serotonin (5-hydroxytryptamine, 5-HT) autoreceptors may desensitize during prolonged administration of antidepressant drugs. If autoreceptors desensitize, their inhibitory influence on extracellular 5-HT should be attenuated. To test this hypothesis, the selective serotonin reuptake inhibitor (SSRI) citalopram (10 mg kg(-1), s.c., b.i.d.) or saline was administered for 14 days to rats. After a 24-h washout period, rats were anesthetized, and implanted with dialysis probes for determination of 5-HT in the frontal cortex (FCx) and dorsal hippocampus (DH). In response to citalopram (5 mg kg(-1), s.c.) challenge, there were moderate increases in 5-HT in the FCx and DH of both the chronic citalopram and saline pretreatment groups. After subsequent administration of the 5-HT(1A/1B) autoreceptor antagonist, (-)-penbutolol, there were further increases in 5-HT in the FCx and DH of the saline pretreatment group. Moreover, contrary to the expected effect if autoreceptors were desensitized, the potentiation produced by (-)-penbutolol was greater in the FCx and DH of the chronic citalopram group as compared to rats pretreated with saline. These results suggest that autoreceptors still restrain the increase in 5-HT produced by an SSRI after prolonged administration.     

Effects of fluoxetine administration on mu-opoid receptor immunostaining in the rat forebrain

Fluoxetine is a selective serotonin reuptake inhibitor. Analysis of mu-opioid receptor immunostaining after chronic fluoxetine administration in rats revealed an increase in the density of cells expressing mu-opioid receptors in the caudatus-putamen, the dentate gyrus, the lateral septum and the frontal, parietal and piriform cortices. These data suggest that mu-opioid receptor expression in the rat forebrain is altered by in vivo chronic fluoxetine treatment.     

Hypericum LI 160 inhibits uptake of serotonin and norepinephrine in astrocytes

Extracts of Hypericum perforatum, commonly known as St. John's wort, are frequently used in Germany and other European countries to treat mild to moderately severe depression, but the mechanism of antidepressant activity of Hypericum is not understood. Because known mechanisms of antidepressant activity include inhibition of serotonin and/or norepinephrine uptake, we investigated the effects of standardized extracts of Hypericum LI 160 on the transport of these monoamine neurotransmitters into astrocytes, cells which surround synaptic terminals and regulate neurotransmission by means of their uptake systems. We found that LI 160 inhibited both serotonin and norepinephrine uptake in a dose-dependent manner. The two monoamine transport systems were affected differently by LI 160: for serotonin, the main effect was a 50% decrease in the rate of maximal transport, whereas for norepinephrine, the main effect was a 4.5 fold reduction in the apparent affinity of norepinephrine for its uptake sites. Upon removal of LI 160, uptake was restored, thereby indicating that the inhibition was not due to a toxic effect of Hypericum on the cells. These findings suggest that the ability of LI 160 to inhibit serotonin and norepinephrine uptake may underlie the antidepressant activity of this Hypericum extract.     

特质焦虑和防御功能对抗抑郁药疗效的影响

目的研究特质焦虑与防御功能之间的关系,以及两者协同作用对抗抑郁药治疗效果的影响。方法选取102例首发的抑郁症病人,给予艾司西酞普兰治疗,应用17项汉密尔顿抑郁量表（HAMD-17）、状态-特质焦虑问卷（STAI）和88项防御方式问卷调查（DSQ-88）,于治疗前后进行评分。结果最终有84例完成了本研究。特质焦虑分值较高和总体防御功能（ODF）水平低的病人,其最终的汉密尔顿抑郁量表的评分较高。结论高水平的特质焦虑与不成熟的防御功能协同作用,对抗抑郁药的疗效有明显的负性影响。     

Brief Clinical Report REDUCTION OF CENTRAL POSTSTROKE PAIN WITH THE SELECTIVE SEROTONIN REUPTAKE INHIBITOR FLUVOXAMINE

To investigate the effect of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine on central poststroke pain (CPSP), fluvoxamine (25 to 125 mg daily) was given to 31 patients. Although 3 patients dropped out within 1 week, 28 patients who received fluvoxamine for 2 to 4 weeks showed a significant reduction in the visual analog scale (VAS) for pain from 7.7 &#45 2.2 to 6.0 &#45 3.4 (p <. 01). This improvement in VAS was significant in patients within less than 1 year after stroke, but not in those with a duration of more than 1 year. Zung s Self-rating Depression Scale (SDS) was also significantly improved after treatment, but there was no significant correlation between the changes in VAS and SDS. Although this is not a double-blind, placebo-controlled trial, these results suggest that fluvoxarnine is useful for the control of CPSP regardless of depression when used relatively early after stroke.