Desmethylimipramine attenuates cocaine withdrawal in rats

Depression and anhedonia are two major symptoms of cocaine withdrawal in humans. Hence, pharmacological treatments effective in depression might also alleviate the symptoms of cocaine withdrawal. In the present study, the effects of acute and repeated administration of a tricyclic antidepressant, desmethylimipramine (DMI), were investigated in naive and cocaine-withdrawing rats. An animal model of cocaine withdrawal was used that employs the elevation in intracranial self-stimulation (ICSS) thresholds following the termination of prolonged periods of cocaine self-administration as a measure of an animal's anhedonic state. The influence of chronic DMI treatment on-adrenergic receptor binding and affinity was also correlated with the behavioral signs of cocaine withdrawal. Neither acute nor repeated DMI treatment influenced reward functions in rats that were not undergoing cocaine withdrawal. However, repeated DMI treatment significantly down-regulated-adrenergic receptors, and shortened the duration of the post-cocaine anhedonia (elevation in thresholds). Furthermore, the magnitude of the-adrenergic receptor down-regulation correlated significantly with the degree of effectiveness of DMI treatment in reversing the post-cocaine anhedonia. However, chronic DMI treatment did reduce the amount of cocaine self-administered by the animals. The reversal of the post-cocaine anhedonia in this animal model of cocaine withdrawal by chronic DMI treatment demonstrates the potential usefulness of the model in identifying new pharmacotherapies for cocaine withdrawal. In addition, the results indicate that tricyclic antidepressants may be able to ameliorate some of the symptoms of cocaine withdrawal.     

Anxiety- and depressive-like profiles during early- and mid-adolescence in the female Wistar Kyoto rat

Approaches for the development of preclinical models of depression extensively use adult and male animals owing to the discrepancies arising out of the hormonal flux in adult females and adolescents during attainment of puberty. Thus the increased vulnerability of females towards clinical depression and anxiety-related disorders remains incompletely understood. Development of clinical models of depression in adolescent females is essential in order to evolve effective treatment strategies for adolescent depression. In the present study, we have examined the anxiety and depressive-like profiles in a putative animal model of childhood depression, the Wistar Kyoto (WKY) rat, during early adolescence (∼postnatal day 30) and mid-adolescence (∼postnatal day 40). Female adolescent WKY rats, tested on a series of behavioural tests modelling anxiety- and depressive-like behaviours with age-matched Wistars as controls, demonstrated marked differences during early adolescence in a strain- and age-specific manner. Anxiety indices were obtained from exposure to the elevated plus maze, where social communication vide 50-kHz ultrasonic vocalizations was also assessed, while immobility and other parameters in the forced swim test were screened for depressive-like profiles. Sucrose preference, used as a measure of anhedonia in animals, was lower in WKYs at both ages tested and decreased with age. Anxiety-related behaviours were prominent in WKY rats only during early adolescence. WKY female rats are anxious during early adolescence and exhibit anhedonia as a core symptom of depression during early- and mid-adolescence, thus indicating that inclusion of female animals in preclinical trials is essential and will contribute to gender-based approaches to diagnosis and treatment of adolescent depression in females.     

Amelioration of neurobehavioral and cognitive abilities of F1 progeny following dietary supplementation with Spirulina to protein malnourished mothers

Early life adversities (stress, infection and mal/undernutrition) can affect neurocognitive, hippocampal and immunological functioning of the brain throughout life. Substantial evidence suggests that maternal protein malnutrition contributes to the progression of neurocognitive abnormalities and psychopathologies in adolescence and adulthood in offspring. Maternal malnutrition is prevalent in low and middle resource populations. The present study was therefore undertaken to evaluate the effects of dietary Spirulina supplementation of protein malnourished mothers during pregnancy and lactation on their offspring’s reflex, neurobehavioral and cognitive development. Spirulina is a Cyanobacterium and a major source of protein and is being used extensively as a dynamic nutraceutical against aging and neurodegeneration. Sprague Dawley rats were switched to low protein (8% protein) or normal protein (20% protein) diet for 15 days before conception. Spirulina was orally administered (400 mg/kg/b.wt.) to subgroups of pregnant females from the day of conception throughout the lactational period. We examined several parameters including reproductive performance of dams, physical development, postnatal reflex ontogeny, locomotor behavior, neuromuscular strength, anxiety, anhedonic behavior, cognitive abilities and microglia populations in the F1 progeny. The study showed improved reproductive performance of Spirulina supplemented protein malnourished dams, accelerated acquisition of neurological reflexes, better physical appearance, enhanced neuromuscular strength, improved spatial learning and memory and partly normalized PMN induced hyperactivity, anxiolytic and anhedonic behavior in offspring. These beneficial effects of Spirulina consumption were also accompanied by reduced microglial activation which might assist in restoring the behavioral and cognitive skills in protein malnourished F1 rats. Maternal Spirulina supplementation is therefore proposed as an economical nutraceutical/supplement to combat malnutrition associated behavioral and cognitive deficits.     

中文版修订社会快感缺失量表的信效度

目的 分析中文版修订社会快感缺失量表（RSAS-C）的信度和效度.方法 采用RSAS-C对314名正常健康者和204名精神分裂症患者进行评估,随机抽取75名正常者和102名患者间隔两周后进行重测,评估重测信度,以多伦多述情障碍量表（TAS-20）总分和阳性与阴性症状量表（PANSS）的阴性症状分为效标,计算效标关联效度.结果 信度检验：总样本、患者组和正常组RSAS-C的Cronbach α系数分别为0.787、0.804和0.759;分半信度分别为0.715、0.740和0.676;重测信度分别为0.902、0.916和0.831.效度检验：总样本、患者组和正常组RSAS-C得分与TAS-20总分间的相关系数分别为0.261、0.398和0.154,患者组RSAS-C得分与PANSS阴性症状分的相关系数为0.303,差异有统计学意义（均P＜0.01）.精神分裂症患者RSAS-C得分显著高于正常健康者,表明RSAS-C具有较好的实证效度.结论 RSAS-C有较好的信度和效度,可用于中国正常人群和精神分裂症患者人群快感缺失状况的评估.     

Chronic mild stress-induced anhedonia: A realistic animal model of depression

Chronic sequential administration of a variety of mild stressors causes a decrease in responsiveness to rewards in rats, which is reversed by chronic administration of antidepressant drugs. This paper reviews the validity of chronic mild stress-induced anhedonia as an animal model of depression, and the evidence that changes in hedonic responsiveness in this model are mediated by changes in the sensitivity of dopamine D2 receptors in the nucleus accumbens. The review opens with an analysis of the design features of animal models of depression, and ends with a brief account of other animal models of anhedonia.     

Evaluation of the effects of chronic mild stressors on hedonic and physiological responses: sex and strain compared

The chronic mild stress (CMS) paradigm was developed in order to simulate in animals the symptom of anhedonia, a major feature of depression. Typically, changes in hedonic status are interpreted from a decrease in either intake or preference for a mild sucrose solution. Although the incidence of clinical depression is significantly higher in women than in men, the study of this disorder in most animal models of depression has been based on the responses of male rodents. The purpose of this study was to compare the effects of 6 weeks of CMS administration among male and female rats of two rat strains, Sprague-Dawley (SD) and Long Evans (LE), with respect to physiological (body, adrenal gland, and spleen weight) and biochemical (plasma corticosterone levels) indices of stress as well as evaluations of 1 and 24 h sucrose intake and preference. Estrous cycle was tracked throughout the study. Overall, our results indicate a slower rate of weight gain in animals, greater in males, exposed to the chronic stressor regime. Furthermore, CMS is shown to disrupt estrous cycling, predominantly in the Long Evans strain of rats. The main behavioral finding was a significant reduction in 24 h sucrose intake in female treated groups, which was not accompanied by alterations in preference. Corticosterone levels were elevated in CMS-treated animals relative to the singly housed control groups, but exposure to a subsequent stressor was not influenced by the stress history. Taken together, the effects of chronic stressor exposure are evident, based on physiological and biochemical indices, although none of the measures distinguished any striking gender specific reactions. The usefulness of sucrose intake or preference as behavioral indices of CMS-induced anhedonia in males and females is modest at best.