脑梗死后抑郁与负性生活事件相关性研究

目的　探讨脑梗死后抑郁与负性生活事件的关系。方法　将脑梗死患者按是否受负性生活事件影响分为 A(n=75 )、B(n=73)两组。采用抑郁自评量表 (SDS)及 Hamilton抑郁量表筛查 ,对两组进行比较分析 ,并观察其治疗效果。结果　A、B两组脑梗死后抑郁的发生率分别为 5 6 %、38.4 % ,两者比较差异显著 (P<0 .0 5 ) ;百忧解可显著改善或治愈脑梗死后抑郁 ,总有效率 6 1.7%。结论　脑梗死后抑郁发生与负性生活事件相关。百忧解治疗有效     

Prolonged but not acute fluoxetine administration produces its inhibitory effect on hippocampal seizures in rats

This study assessed the effects of acute as well as long-term administration of fluoxetine, a selective serotonin (5-HT) reuptake inhibitor with anti-depressant properties, on hippocampal (HIP) seizures elicited by electrical stimulation in rats. The fluoxetine effect on HIP seizures was also assessed following long-term treatment with gepirone, a 5-HT_1A receptor agonist. Acute single administration of fluoxetine (1, 10 mg/kg; IP) was found to produce no significant effect on HIP seizure activity. Following daily IP administration of fluoxetine (10 mg/kg per day) or gepirone (10 mg/kg per day) for 21 days, animals were given a 7-day drug-free period and then challenged with an acute dose of 10 mg/kg fluoxetine. These treatment regimens resulted in a significantly increased afterdischarge threshold of HIP seizures in response to acute fluoxetine administration. The inhibitory effect of fluoxetine, however, was not present 4 weeks after long-term treatment with either fluoxetine or gepirone. The present results indicate that long-term treatment with these compounds enhances the antiepileptic effect of subsequent fluoxetine administration on the generation of HIP seizures. This effect is possibly related to the well-demonstrated evidence that fluoxetine and gepirone, on long-term treatment, facilitate net 5-HT neurotransmission through desensitization of presynaptic 5-HT autoreceptors.     

A Study of Fluoxetine in Obese Elderly Patients with Type 2 Diabetes

In order to establish the safety and efficacy of fluoxetine in subjects over 60 years of age with Type 2 diabetes, a randomized, double-blind, parallel study of 30 obese subjects was undertaken, comparing the use of fluoxetine 60 mg daily with placebo. Subjects were diet controlled with an HbA₁ < 14% (reference range 6–9%) and BMI > 29 kg m². Those taking fluoxetine had a median weight loss of 2.6 kg at 3 months (p < 0.001) and 3.9 kg at 6 months (p < 0–02), compared with weight loss in the placebo group of 0.1 kg and 0.0 kg at 3 and 6 months, respectively. Improved glycaemic control was also demonstrated in the fluoxetine group compared with placebo, initial HbA₁ levels of 8.0% vs 8.7% (NS) falling at 4 months by 0.9% (p < 0.02) and at six months by 0.9% (p < 0.02). No sustained improvement in fasting blood glucose levels was demonstrated. Reporting of adverse events was similar in both groups. Fluoxetine in the short term aids weight loss and improves glycaemic control without a significant increase in adverse events in elderly Type 2 diabetic subjects.     

Behavioural analysis of the anorectic effects of fluoxetine and fenfluramine

Two sets of experiments were carried out to compare the effects of fenfluramine and fluoxetine on consummatory and operant behaviour. In food-deprived rats allowed access to a 35% sucrose solution, an initial period of sucrose consumption was followed by a short period of grooming and exploratory behaviour, later superceded by resting. This behavioural satiety sequence was advanced by fluoxetine, but disrupted bydl-fenfluramine, which suppressed post-prandial resting, even at sub-anorectic doses. Fluoxetine also elicited resting behaviour following water drinking. However, this did not appear to be a non-specific sedative effect, since fluoxetine increased post-prandial grooming. In rats performing on random interval schedules of food reinforcement, fluoxetine caused proportionally greater decreases in responding on a reinforcement-lean schedule (RI-300s), as compared to a reinforcement-rich schedule (RI-7.5s); this effect is similar to that of a reduction in level of food deprivation. By contrast, fenfluramine reduced responding equally on both schedules. In both paradigms, the effects of fluoxetine were compatible with an increase in postprandial satiety, but the effects of fenfluramine were not.     

百忧解治疗痉挛性斜颈的效果和机理探讨

目的探讨百忧解治疗痉挛性斜颈的疗效和机理.方法分析6例痉挛性斜颈的治疗过程.结果6例病人应用百忧解治疗均有效果.结论百忧解治疗痉挛性斜颈是有效的,其发病可能与5-羟色胺浓度降低有关.     

Up-regulation of β1-adrenergic receptors in rat brain after chronic citalopram and fluoxetine treatments

Quantitative receptor autoradiography was used to study the effects of the selective serotonin reuptake inhibitors citalopram and fluoxetine and the tricyclic antidepressant imipramine on the regulation of ₁-adrenergic receptors in the rat brain. Rats were treated with saline, citalopram (10 mg kg^–1), fluoxetine (10 mg kg^–1), or imipramine (15 mg kg^–1) SC once daily for 14 days. [¹²⁵I]Iodocyanopindolol binding to ₁-adrenergic receptors was found to increase significantly in the caudate-putamen and the somatosensory areas of the frontal cortex after both citalopram and fluoxetine treatments. Imipramine treatment elicited a marked decrease in ₁ binding in the outer laminae of the cingulate cortex, as well as in the motor and somatosensory areas of the frontal cortex. In a separate experiment, rats were treated with saline, citalopram (2.5, 10 and 20 mg kg^–1) or fluoxetine (2.5, 10 and 20 mg kg^–1) SC once daily for 14 days. The effects of citalopram and fluoxetine on ₁ receptors in the somatosensory cortex and caudate-putamen were replicated. These results demonstrate that chronic administration of selective serotonin reuptake inhibitors, in contrast to imipramine, can cause a regional up-regulation of ₁-adrenergic receptors in the rat brain.     

氟西汀治疗抑郁性障碍三期临床验证

目的：验证国产氟西洒汀长期、大范围治疗抑郁性障碍的疗效和副反应。方法：采用国产氟西汀开放治疗抑郁性障碍30例,以HAMD和TESS评定症状、疗效和副反应。结果：氟西汀对各类型抑郁性障碍的疗效肯定;显效率达80％,副反应少且轻。结论：氟西汀是一种安全、有效、广谱的抗抑郁剂。     

Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test

Rationale: The forced swimming test (FST) is a behavioral test in rodents that predicts the clinical efficacy of many types of antidepressant treatments. Recently, a behavior sampling technique was developed that scores individual response categories, including swimming, climbing and immobility. Although all antidepressant drugs reduce immobility in the FST, at least two distinct active behavioral patterns are produced by pharmacologically selective antidepressant drugs. Serotonin-selective reuptake inhibitors increase swimming behavior, while drugs acting primarily to increase extracellular levels of norepinephrine or dopamine increase climbing behavior. Distinct patterns of active behaviors in the FST may be mediated by distinct neurotransmitters, but this has not been shown directly. Objectives: The present study examined the role of serotonin in mediating active behaviors in the forced swimming test after treatment with two antidepressant drugs, the selective serotonin reuptake inhibitor, fluoxetine and the selective norepinephrine reuptake inhibitor, desipramine. Methods: Endogenous serotonin was depleted by administering para-cholorophenylalanine (PCPA, 150 mg/kg, IP.) to rats 72 h and 48 h prior to the swim test. Fluoxetine (10 mg/kg, SC) or desipramine (10 mg/kg, SC) was given three times over a 24-h period prior to the FST. Behavioral responses, including immobility, swimming and climbing, were counted during the 5-min test. Results: Pretreatment with PCPA blocked fluoxetine-induced reduction in immobility and increase in swimming behavior during the FST. In contrast, PCPA pretreatment did not interfere with the ability of desipramine to reduce immobility and increase climbing behavior. Conclusions: Depletion of serotonin prevented the behavioral effects of the selective serotonin reuptake inhibitor fluoxetine in the rat FST. Furthermore, depletion of serotonin had no impact on the behavioral effects induced by the selective norepinephrine reuptake inhibitor, desipramine. The effects of antidepressant drugs on FST-induced immobility may be exerted by distinguishable contributions from different neurotransmitter systems. Received: 4 February 1999 / Final version: 2 June 1999     

l-Sulpiride, at a low, non-neuroleptic dose, prevents conditioned fear stress-induced freezing behavior in rats

Antidepressant drugs are effective in anxiety states, including panic disorder. Both clinical and animal studies indicate that l-sulpiride, at low, non-neuroleptic doses, has antidepressant activity. The present study examined the effect of an antidepressant dose of l-sulpiride (4 mg/kg per day SC), compared with a well-established antidepressant drug (fluoxetine, 3 mg/ kg per day SC), in a rat model of anticipatory anxiety/panic behavior: conditioned fear stress-induced freezing behavior. Long-term (26 days) administration of l-sulpiride almost completely abolished freezing, a similar effect being produced by fluoxetine (freezing duration, in seconds: controls, 148.1 ± 29.6; l-sulpiride, 27.5 ± 8.3; fluoxetine, 72.0 ± 15.2). The same doses of l-sulpiride (4 mg/kg SC) and fluoxetine (3 mg/kg SC) had no effect when administered for shorter periods (1, 5, or 12 days). No effect was produced by the long-term (26 days) administration of a neuroleptic dose of l-sulpiride (20 mg/kg per day SC). These results demonstrate that long-term administration of low, non-neuroleptic doses of l-sulpiride, is highly effective in an animal model of anticipatory anxiety/panic behavior. Received: 13 March 1998/Final version: 23 July 1998     

Withdrawal-like behaviour induced by inhibitors of biogenic amine reuptake in rats treated chronically with Δ 9-tetrahydrocannabinol

The effects of the biogenic amine reuptake inhibitors fluoxetine, clomipramine and imipramine on the behaviour of rats after chronic treatment with ⁹ tetrahydrocannabinol ( ⁹-THC) for 5 and 10 days were examined. Rats with permanently in-dwelling IV cannulae were injected twice daily with doses of ⁹-THC (2–6 mg/kg). ⁹-THC treatment reduced the rate of body weight gain and induced the typical biphasic modifications of behaviour. Tolerance developed to both of these effects. On days 6 and 11 of the experiment, rats were injected IP with 15 mg/kg imipramine HCl, clomipramine HCl or fluoxetine HCl, and behaviour, consisting of writhes, backward kicks, jumps and wet shakes, was observed for the next 30 min. Each of the amine reuptake inhibitors induced changes in behaviour, the severity of which appeared to correlate with their ability to inhibit the reuptake of 5-hydroxytryptamine (5-HT). It is suggested that tryptaminergic mechanisms are involved in the production of a withdrawal-like behaviour after chronic ⁹-THC treatment.