Effect of a selective serotonin uptake inhibitor in agoraphobia with panic attacks. A double-blind comparison of zimeldine, imipramine and placebo

A double-blind clinical trial of zimeldine, a potent inhibitor of central serotonin reuptake, versus imipramine and placebo was carried out on 44 patients suffering from agoraphobia with panic attacks. Zimeldine was a superior treatment on all rating scales other than a global rating scale which did not reach statistically significant superiority. Imipramine was not shown to be superior to placebo. The implications of these results for further research on the underlying pathophysiology of agoraphobia with panic attacks are discussed.     

Release of 3H-noradrenaline from the rat vas deferens under various in vitro conditions

The release of ³H-(-)-noradrenaline (NA) from rat vas deferens in vitro was examined under various experimental conditions. It was found that in normal and reserpinized vas deferens the release of NA evoked by (+)-amphetamine (5 times 10^?6 M) or low external Na⁺ (26 mM) was antagonized by imipramine methiodide and desipramine, inhibitors of the NA uptake, but was not dependent on the presence of Ca²⁺ in the medium and was not antagonized by the potent local anaesthetic agent bethoxycaine. The release evoked by veratridine in reserpinized tissue was antagonized by the uptake inhibitors but was in normal tissue only partially inhibited in presence of Ca²⁺ but almost completely in absence of Ca²⁺. The release by high K⁺ (117 mM) + low Na⁺ (26 mM) in normal tissue was dependent on the presence of Ca²⁺ and was antagonized by the muscarinic agonists carbacholine and metacholine and by high concentrations of desipramine. In the reserpinized vasa the corresponding release was not dependent on Ca²⁺ and was not antagonized by the muscarinic agents but was inhibited by high concentrations of desipramine.     

Repeated imipramine treatment increases the responsivity of the rat hippocampus to dopamine. Anin vitro study

Summary The sensitivity of hippocampal neurons to dopamine was studied in hippocampal slices obtained from rats treated acutely (10 mg/kg) or repeatedly (10 mg/kg, 14 days, twice a day) with imipramine. In non-treated rats dopamine induced a slight excitation or depression of the firing rate of CA 1 pyramidal neurons in slice preparations. Hippocampal slices prepared from the imipramine-treated rats displayed greater changes in the firing rate after dopamine application. Repeated imipramine administration also increased the number of slices sensitive to dopamine. it is concluded that repeated imipramine administration induces supersensitivity of hippocampal dopamine receptors.     

Attenuation by chronic imipramine treatment of [H]clonidine binding to cortical membranes and of clonidine-induced hypothermia: the influence of central chemosympathectomy

Central chemosympathectomy with intraventricular injection of 250 μg of 6-hydroxydopamine, resulting in depression of cerebral noradrenaline level by 75%, led to an increase in specific binding of [³H]clonidine to cerebral cortical membranes, but did not affect the hypothermic response to clonidine. Chronic imipramine treatment depressed [³H]clonidine binding and attenuated clonidine-induced hypothermia similarly in non-chemosympathectomized and chemosympathectomized rats.     

Effect of glibenclamide on the osmotic resistance of pancreatic β-cells

The effect of glibenclamide on the osmotic resistance of β-cells was measured using isolated β-cells from ob/ob-mice. The β-cells were incubated at different osmolarity and the diameters of the approximately spherical β-cells were measured at 22°C or at 37°C with the aid of a screw micrometer eyepiece fitted to a light microscope. A near linear decrease of β-cell diameter was found with increasing osmolarity (111–617 mosm/l). Control experiments showed that the membrane stabilizers, imipramine (0.1 mmol/l) or tetracaine (I mmol/l), strongly reduced the osmotic swelling induced by low osmolarity (180 mosm/l). Glibenclamide (0.001 or 0.2 mmol/l) did not affect the β-cell diameter at normal osmolarity (317 mosm/l) but reduced the swelling induced by hypoosmolarity (180 mosm/l) and the shrinking induced by hyperosmolarity (617 mosm/l). It is suggested that glibenclamide increases the osmotic resistance of isolated β-cells by changing transmembrane flow of ions.     

Reduction in hippocampal neurogenesis after social defeat is long-lasting and responsive to late antidepressant treatment

Major depressive disorder is a chronic disabling disease, often triggered and exacerbated by stressors of a social nature. Hippocampal volume reductions have been reported in depressed patients. In support of the neurogenesis theory of depression, in several stress‐based animal models of depression, adult hippocampal neurogenesis was reduced and subsequently rescued by parallel antidepressant treatment. Here, we investigated whether repeated social defeat and subsequent individual housing for 3 months induces long‐lasting changes in adult hippocampal neurogenesis in rats, and whether these can be normalized by late antidepressant treatment, as would match human depression. Neurogenesis was analysed by stereological quantification of the number of immature doublecortin (DCX)‐immunopositive cells, in particular young (class I) and more mature (class II) DCX⁺ cells, to distinguish differential effects of stress or drug treatment on these subpopulations. Using this social defeat paradigm, the total DCX⁺ cell number was significantly reduced. This was most profound for older (class II) DCX⁺ cells with long apical dendrites, whereas younger, class I cells remained unaffected. Treatment with the broad‐acting tricyclic antidepressant imipramine, only during the last 3 weeks of the 3‐month period after social defeat, completely restored the reduction in neurogenesis by increasing both class I and II DCX⁺ cell populations. We conclude that despite the lack of elevated corticosterone plasma levels, neurogenesis is affected in a lasting manner by a decline in a distinct neuronal population of more mature newborn cells. Thus, the neurogenic deficit induced by this social defeat paradigm is long‐lasting, but can still be normalized by late imipramine treatment.     

Nitric oxide modulation in protective role of antidepressants against chronic fatigue syndrome in mice

Background and Objective:

The present study was designed to elucidate the possible nitric oxide (NO) mechanism in the protective effect of antidepressants using mice model of chronic fatigue syndrome (CFS).

Materials and Methods:

Male albino laca mice were forced to swim for each 6 min session for 7 days and immobility period was measured on every alternate day (1^st, 3^rd, 5^th, 7^th). After 7 days various behavioral tests (locomotor, mirror chamber, and plus maze tests for anxiety) were performed and biochemical estimations (lipid peroxidation, nitrite levels, GSH (reduced glutathione), and catalase activity) in mice brain were performed. Animals were pretreated with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) daily for 7 days.

Results:

The present study showed that continued forced swimming for 7 days caused chronic fatigue-induced anxiety-like behavior as assessed in mirror chamber, plus maze tests, and impairment in locomotor activity followed by oxidative damage (as evidenced by increased lipid peroxidation, nitrite levels, depleted reduced glutathione, and catalase activity) in animals. Seven days pretreatment with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) significantly improved behavioral and biochemical alterations. Further, L-nitro-arginine methyl ester (L-NAME,5 mg/kg) and methylene blue (MB, 10 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) potentiated their protective effect. However, l-arginine (100 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) reversed their protective effect as compared with their effect per se (P < 0.05).

Conclusion:

The present study suggests that protective effect of citalopram and imipramine might be due to its NO modulation against chronic fatigue induced behavioral and biochemical alterations.     

Early life handling decreases serotonin turnover in the nucleus accumbens and affects feeding behavior of adult rats

In our previous studies, we reported that neonatally handled rats have an increased ingestion of sweet food but are resistant to the damaging effects of a chronic exposure to a highly palatable diet. Accumbal serotonin (5‐HT) is important for feeding behavior and plays a role in the vulnerability to diet‐induced obesity. Therefore, our hypotheses were (1) 5‐HT turnover in the nucleus accumbens is altered in neonatally handled animals and plays a role in their differential feeding behavior and (2) if this is so, a chronic pharmacological treatment affecting 5‐HT reuptake (chronic imipramine) would be able to revert the behavioral findings. Litters were divided into nonhandled and handled (10 min/day, Days 1–10 after birth). In Experiment 1, we demonstrated that a decreased 5‐HT metabolism in the nucleus accumbens was observed in adult handled animals. In Experiment 2, the two previous groups were subdivided and assigned to receive imipramine diluted in water or water alone. After 30 days of treatment, we evaluated their weight gain and feeding behavior. Handled rats weighed less than nonhandled rats, and all imipramine‐treated rats showed a reduction in weight gain after 60 days of treatment. Imipramine reverted the increased sweet food consumption seen in neonatally handled rats. We conclude that serotonin is involved in the altered feeding behavior of neonatally handled rats, and this protocol is an important tool for studying the mechanisms by which early life events have a long‐term impact on feeding preferences. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52:190–196, 2010     

米安色林与丙咪嗪治疗抑郁症的临床对照研究

目的 评价米安色林与丙咪嗪治疗抑郁症的临床疗效和安全性。方法 将51例符合CCMD-3抑郁症诊断标准的抑郁症患者随机分为两组，分别给予米安色林和丙咪嗪治疗，于治疗前和治疗后1，2，4，6周末分别采用汉密尔顿抑郁量表（HAMD量表）、临床疗效总体评定量表及不良反应量表评定。结果 米安色林与丙咪嗪总体疗效相似（P〉0．05）；米安色林组治疗第1周就起效；治疗前与治疗后比较，HAMD评分两组均有显著性差异（P〈0．01），两组之间则无显著性差异（P〉0．05），米安色林组的不良反应少于丙咪嗪组。结论米安色林是一种安全有效的新一代抗抑郁药物，适用于伴有失眠症状的老年抑郁症患者。