OBJECTIVE: The aims of the present study were to explore the behavioural effects and to understand the possible mode of action of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced depressive model and the biochemical alterations such as brain derived neurotrophic factor (BDNF), Akt, cyclic-AMP response element binding (CREB) protein level in the hippocampus of rats. METHODS: We examined the effects of chronic administration of BME on CUS exposed rats for 28 days. Behavioural changes were assessed by sucrose consumption and open field test to assess the effect of BME on CUS-induced depression. The mechanisms underlying antidepressant like action of BME was further evaluated by measuring levels of BDNF, Akt, and CREB in the hippocampus of rat brain and compared with the standard tricyclic antidepressant drug imipramine (20 mg/kg body weight). RESULTS: Exposure to CUS for 28 days produced depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity including decreased BDNF, Akt and CREB levels in the hippocampus. Daily administration of BME at a dose of (80 mg/kg body weight) significantly reverses the behavioral alteration and restored the normal level of BDNF, total and phospho-Akt, total and phospho CREB in the hippocampus of CUS induced rats as compared to vehicle treated control rats. CONCLUSION: These findings suggest that BME ameliorates CUS induced behavioural depression in rats and that can be used as a potent therapeutic agent in treating depressive like behavior.
Animals ; Bacopa* ; Brain ; Brain-Derived Neurotrophic Factor* ; Depression ; Hippocampus* ; Imipramine ; Motor Activity ; Rats* ; Response Elements ; Sucrose

Nocturnal enuresis is a common problem of children during sleeping at preschool or school age. It may affect negatively the psychosocial development of children. Children with enuresis may have lower self-esteem and lower quality of life. There are three main factors of the pathophysiology of enuresis: high nocturnal urine production, nocturnal low bladder capacity or increased detrusor muscle activity, and arousal disorder. As pharmacological therapy for nocturnal enuresis, several medications including desmopressin, anticholinergics, imipramine have been used for a long time. As first-line therapy, desmopressin combined with anticholinergics has good response in primary monosymptomatic nocturnal enuresis. Because imipramine has serious and lethal cardiotoxic effect with overdosage, imipramine should be prescribed after EKG to rule out the conduction problem of heart.
Arousal ; Child ; Cholinergic Antagonists ; Deamino Arginine Vasopressin ; Electrocardiography ; Enuresis ; Heart ; Humans ; Imipramine ; Nocturnal Enuresis* ; Quality of Life ; Urinary Bladder

The aim of the present study was to investigate the effects of ketamine, imipramine, and ketamine plus imipramine on chronic depression-like behaviors of Wistar Kyoto (WKY) rats and underlying mechanism. Six-week-old Wistar rats were used as normal control. WKY rats, depression model animal, were injected intraperitoneally with ketamine (1 week, replaced with saline in 2(nd) week), imipramine (2 weeks), or ketamine in combination with imipramine. The depression-like behaviors were assessed by sucrose preference and forced swimming tests. Protein expressions of β form of calcium/calmodulin-dependent protein kinase type II (βCaMKII) and membrane fraction of glutamate receptor 1 (GluR1) were measured in corresponding brain tissue with Western blot. The results showed that, compared with Wistar rats, WKY rats exhibited decreased sucrose preference and extended immobility time. Ketamine alone did not affect depression-like behaviors of WKY, whereas imipramine or its combination with ketamine could significantly decrease the immobility time. Compared with Wistar rats, WKY rats showed up-regulated levels of βCaMKII and membrane GluR1 protein expressions in habenula, and down-regulated level of membrane GluR1 protein expressions in the prefrontal cortex. Imipramine or its combination with ketamine could reverse these changes of protein expressions in WKY rats. There was no difference in reversing effect between imipramine and its combination with ketamine. Ketamine alone did not affect the βCaMKII and membrane GluR1 protein expressions in the habenula, but increased membrane GluR1 protein expression in the prefrontal cortex of WKY rats. These results suggest 2-week imipramine treatment significantly improves depressive behavior in WKY rats; however, the addition of ketamine in the first week fails to enhance the effect of imipramine. The underlying mechanisms of imipramine's anti-depressive effect may be associated with the down-regulation of βCaMKII and membrane GluR1 in the habenula, as well as the up-regulation of membrane GluR1 in the prefrontal cortex.
Animals ; Brain ; Depression ; Depressive Disorder ; Disease Models, Animal ; Down-Regulation ; Imipramine ; Ketamine ; Male ; Rats ; Rats, Inbred WKY ; Swimming ; Up-Regulation

BACKGROUND: We examined the usefulness of urine osmolality, as a predictive factor in the treatment of monosymptomatic nocturnal enuresis (NE) with combination therapy of imipramine and desmopressin. METHODS: From May 2014 to April 2015, 59 monosymptomatic NE patients participated in this study. Early morning urine osmolality was measured at 1 week and 1 day before combination therapy of imipramine and desmopressin, and at 1 week and 2 weeks after therapy. The response to combination therapy was evaluated at 3 months after treatment. The mean period of combination therapy was 6.4+/-4.2 weeks. Therapeutic response was classified as complete (0-1 wet night/week), partial (over 50% reduction of night) and non-responders (less than 50% reduction of night). RESULTS: The cumulative rate of the complete and partial responders was 76.3%. Among the 3 groups, the statistically lowest value of pre-treatment urine osmolality was observed in the complete responder group (p<0.001). Urine osmolality increased in all groups after treatment, however, statistically the greatest difference between pre and post-treatment urine osmolality was observed in the complete responder group (p=0.024). No serious side effects were observed. CONCLUSION: Early morning urine osmolality and change of urine osmolality between pre and post-treatment have predictive values in the response to combined imipramine and desmopressin for treatment of monosymptomatic NE.
Deamino Arginine Vasopressin* ; Enuresis ; Humans ; Imipramine* ; Nocturnal Enuresis* ; Osmolar Concentration*

Antidepressants are clinically used for patients with major depression. Antidepressant treatments in certain groups of patients are effective for relieving depression as well as anxiety disorder. However, it is not clearly known whether the use of current antidepressants in healthy persons is beneficial for upcoming depression- and anxiety-inducing life events. To address this question, normal mice were intraperitoneally administered with imipramine or fluoxetine for more than 2 weeks, and behaviors related to anxiety and depression were evaluated. Mice treated with imipramine or fluoxetine for more than 14 days exhibited significantly decreased immobility time in the forced swim test and tail suspension test, but these mice exhibited enhanced anxiety in several behavioral tests. Furthermore, chronic antidepressant treatments followed by sub-threshold level of stress in normal mice profoundly aggravated antidepressant-induced anxiety-like behaviors without further affecting depression-related behaviors. Chronic antidepressant treatments followed by sub-threshold level of stress produced swollen vesicles and ulcerations on the lips as well as a watery and inflammatory nose. Mice given chronic antidepressant treatments displayed intestinal abnormalities evidenced by a highly enlarged and inflamed small intestine full of defecation materials. These results suggest that chronic antidepressant treatment in normal mice provokes anxiety-like behaviors and impairs their stress-coping ability.
Animals ; Antidepressive Agents ; Anxiety Disorders ; Anxiety* ; Defecation ; Depression ; Fluoxetine ; Hindlimb Suspension ; Humans ; Imipramine ; Intestine, Small ; Lip ; Mice* ; Nose ; Ulcer

Cedrus deodara (Pinaceae) has been used traditionally in Ayurveda for the treatment of central nervous system disorders. 3,4-bis(3,4-dimethoxyphenyl)furan-2,5-dione (BDFD) was isolated from heart wood of Cedrus deodara and was shown to have antiepileptic and anxiolytic activity. Thus, the present study was aimed to explore its anti-depressant effect and to correlate the effect with serotonin and nor adrenaline levels of brain. Albino mice were used as experimental animal. Animals were divided in to three groups; vehicle control, imipramine (30 mg/kg i.p.), BDFD (100 mg/kg i.p.). Tail suspension test (TST) and forced swim test (FST) was performed to evaluate antidepressant effect of BDFD. BDFD (100 mg/kg, i.p.) showed a significant decrease in immobility time when subjected to FST whereas immobility time was not significantly altered in TST. BDFD treatment increased serotonin and noradrenaline levels in the brain which is indicative of BDFD having possible atypical antidepressant action.
Animals ; Brain ; Cedrus* ; Central Nervous System Diseases ; Epinephrine ; Heart* ; Hindlimb Suspension ; Imipramine ; Mice ; Norepinephrine ; Rodentia* ; Serotonin ; Wood*

Cyclic vomiting syndrome is characterized by recurrent episodes of stereotyped vomiting separated by regular symptom-free periods. We describe a case of cyclic vomiting syndrome developed after stroke, which has not been reported to date. A 69-year-old woman experienced recurrent vomiting following left cerebral infarct. The patient's vomiting pattern was consistent with cyclic vomiting syndrome, and the diagnosis of cyclic vomiting syndrome was established by exclusion of other known disorders which could have resulted in vomiting. She was treated with imipramine hydrochloride and her symptom was well controlled.
Aged ; Female ; Humans ; Imipramine ; Stroke ; Vomiting

Chronic behavioral stress is a risk factor for depression. To understand chronic stress effects and the mechanism underlying stress-induced emotional changes, various animals model have been developed. We recently reported that mice treated with restraints for 2 h daily for 14 consecutive days (2h-14d or 2hx14d) show lasting depression-like behavior. Restraint provokes emotional stress in the body, but the nature of stress induced by restraints is presumably more complex than emotional stress. So a question remains unsolved whether a similar procedure with "emotional" stress is sufficient to cause depression-like behavior. To address this, we examined whether "emotional" constraints in mice treated for 2hx14d by enforcing them to individually stand on a small stepping platform placed in a water bucket with a quarter full of water, and the stress evoked by this procedure was termed "water-bucket stress". The water-bucket stress activated the hypothalamus-pituitary-adrenal gland (HPA) system in a manner similar to restraint as evidenced by elevation of serum glucocorticoids. After the 2hx14d water-bucket stress, mice showed behavioral changes that were attributed to depression-like behavior, which was stably detected >3 weeks after last water-bucket stress endorsement. Administration of the anti-depressant, imipramine, for 20 days from time after the last emotional constraint completely reversed the stress-induced depression-like behavior. These results suggest that emotional stress evokes for 2hx14d in mice stably induces depression-like behavior in mice, as does the 2hx14d restraint.
Animals ; Anxiety ; Depression ; Glucocorticoids ; Imipramine ; Mice ; Risk Factors ; Stress, Psychological ; Water

OBJECTIVETo study the derivatives of 1,2,4-triazino[5,6-b]indole-3-thione for antidepressant activity in olfactory bulbectomized (OBX) rats. Out of various derivatives tested for acute tail suspension test, the two derivatives showing prominent action were selected for bilateral olfactory bulbectomy model of chronic depression in rats.

METHODSThe sub acute effects of 14-day oral pretreatment of two derivatives labeled as 3a (70 mg/kg) and 3r (70 mg/kg), imipramine (20 mg/kg), fluoxetine (30 mg/kg) and moclobemide (15 mg/kg) were evaluated on bilateral bulbectomy induced rise in body weight, hyperphagia, hyperactivity, and on sexual dysfunction. The serum sodium concentration, body temperature, and heart rate were also recorded.

RESULTSThe derivatives 3a and 3r showed reversal of drop in body weight, reversed OBX induced hyperactivity, normalized body temperature, heart rate, and serum sodium concentration. In elevated maze test, moclobemide, 3a, 3r treatment significantly reduced time spent in open arm as compared to OBX rats. 3a and 3r also improved sexual behavior parameters.

CONCLUSIONSThe present study shows promising antidepressant action and provides a proof of concept for the chronic treatment of 3a, 3r to treat depression.

Acetamides ; pharmacology ; Acetanilides ; pharmacology ; Animals ; Antidepressive Agents ; pharmacology ; Behavior, Animal ; drug effects ; Depression ; drug therapy ; etiology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Fluoxetine ; pharmacology ; Imipramine ; pharmacology ; Male ; Moclobemide ; pharmacology ; Olfaction Disorders ; complications ; pathology ; Olfactory Bulb ; surgery ; Rats ; Rats, Sprague-Dawley ; Triazines ; pharmacology

OBJECTIVE: This study investigated the consensus about treatment strategies for non-responsive and comorbid conditions in panic disorder, which represents one subject addressed by the Korean medication algorithm project for panic disorders 2008. METHODS: The executive committee developed questionnaires about treatment strategies for patients with panic disorder based on guidelines or algorithms and clinical trial studies previously published in foreign countries. This study analyzed the treatment strategies in cases of non-responsive panic disorder and comorbid conditions accompanying panic disorder. Fifty-four (68%) of 80 experts on a committee reviewing panic disorders responded to the questionnaires. We classified the consensus of expert opinions into three categories (first-line, second-line, and third-line treatment strategies) and identified the treatment of choice according using a chi-square test and 95% confidence interval. RESULTS: The consensus about first-line treatment strategies in cases of non-responsive panic disorder included "switch from a selective serotonin reuptake inhibitor to venlafaxine XR or vice versa" and "clonazepam or alprazolam can be combined with another drug even from the initial period". Second-line strategies included tricyclic antidepressants (clomipramine, imipramine) and high dosages of high potency benzodiazepines (alprazolam, clonazepam). The consensus about treatment strategy in cases of comorbid disorders (e.g., depression or other anxiety disorders) recommended antidepressants combined with anxiolytics and cognitive-behavioral therapy as the treatments of choice. Antidepressants combined with anxiolytics were recommended as the first-line strategy, and antidepressant monotherapy and antidepressants combined with cognitive-behavioral therapy emerged as second-line strategies. In cases of comorbid conditions accompanying panic disorder, paroxetine was selected as the treatment of choice. Escitalopram, venlafaxine XR, sertraline, citalopram, alprazolam, and clonazepam were selected as first-line treatments and fluoxetine, mirtazapine, and imipramine were selected as second-line treatments. CONCLUSION: This study provided information about the consensus among Korean experts in regard to treatment strategies for non-responsive panic disorder and comorbid conditions accompanying panic disorder.
Alprazolam ; Anti-Anxiety Agents ; Antidepressive Agents ; Antidepressive Agents, Tricyclic ; Anxiety ; Benzodiazepines ; Citalopram ; Clonazepam ; Comorbidity ; Consensus ; Cyclohexanols ; Depression ; Expert Testimony ; Fluoxetine ; Humans ; Imipramine ; Mianserin ; Panic ; Panic Disorder ; Paroxetine ; Surveys and Questionnaires ; Serotonin ; Sertraline ; Venlafaxine Hydrochloride