Effect of glycine: Studying memory and behavioral changes in mice

Glycine is an important chemical mediator of nervous system that plays a vital role in memory and other neurological functions. Therefore, the effect of glycine on these traits must be studied to understand biological mechanisms of intricate neurological system. We investigated the effect of different doses of glycine on memory and behavior using 30 albino mice models [treated and control]. After two weeks of glycine dosing, we performed light and dark activity and novel-object recognition [NOR] tests to assess the cognitive traits. Brain and blood samples were taken and kept at -70 degree C using ultra-low temperature freezer. Neurochemical estimation of blood glycine level was estimated by high-performance liquid chromatography with electrochemical detectors [HPLC-ECD]. Concentration of glycine [100, 300 and 500 mg/kg] is significantly observed [p<0.01] and it changes due to physiological variations in N-methyl-Daspartate [NMDA] an important neurotransmitter for memory. We observed significant increase in serotonin metabolites including 5-hydroxy tryptophan [5-HT, p<0.05] and 5-hydroxy indole acetic acid [5-HIAA, p<0.001] levels. Similarly, effects were found in case of dopamine [DA, p<0.05] and its metabolites: 3, 4-Dihydroxyphenylacetic acid [DOPAC, p<0.001] and homovanillic acid [HVA, p<0.001]. Histopathological investigation of brain tissues showed cellular clumps at cortical junctions at higher doses of glycine as compared to control. These findings revealed that dose dependent concentration of glycine can be useful for memory loss and behavior deficits

Effects of single administration of apomorphine on memory and monoamine metabolism: a dose related study

In the present study, we have monitored dose dependent effects of apomorphine on learning and memory. Behavioral sensitization and craving, which develop upon repeated treatment with dopamine receptor agonist apomorphine, are major limitations of the therapeutic use of apomorphine in Parkinson's patients. Effects of single [intraperitoneal] injection of apomorphine at different doses [i.e., 0.5, 1.0, and 2.0 mg/ml/kg] on locomotion in a familiar environment [Skinner's box] and memory in Morris water maze were investigated. Results show significantly enhanced activity in Skinner's box in a dose dependant manner. Low dose [0.5 mg/ml/kg] of apomorphine impaired both short- as well as long-term memory while both high and moderate doses of the drug [1.0, and 2.0 mg/ml/kg] enhanced the cognitive profile in rats. However, the memory-enhancing effects of apomorphine at moderate [1.0 mg/ml/kg] dose were more pronounced as compared to high [2.0 mg/ml/kg] dose of the drug. Rats were decapitated on day 2. Whole brains of rats were collected and stored at -70 degree C. Biogenic amines [i.e., 5-Hydroxytryptamine; 5-HT and dopamine] and metabolites [i.e., Dihydroxyphenylacetic acid; DOPAC, Homovanillic acid; HVA and 5-Hydroxyindoleacetic acid; 5HIAA] were estimated by reverse phase High Performance Liquid Chromatography with electrochemical detector [HPLC-EC]. Both low [0.5mg/ml/kg] as well as moderate [1.0mg/ml/kg] dose of apomorphine increased levels of dopamine, DOPAC, HVA, 5-HT and 5-HIAA. Whereas, high [4.0 mg/kg] dose of apomorphine increased levels of dopamine, DOPAC and HVA, while decreased 5-HT and 5-HIAA levels. Results would be helpful in elucidating memory enhancing effects of apomorphine at different doses and its implication for extending therapeutics in cognitive disorders

Repeated treatment with reserpine as a progressive animal model of depression

Treatment-resistant depression is a major health problem worldwide. Restricted validity of the existing animal models of depression along with the need for the study of progressive development of resistance to antidepressants, demands the modeling of a progressive animal model of depression. Present study was designed to test the hypothesis that the repeated administration of reserpine could serve as a progressive animal model of depression. Animals were injected with reserpine [1.0mg/kg; once a day] for three weeks. Results from the present study showed impaired locomotive effects of reserpine in Skinner's box following second as well as third week. These hypolocomotive effects were more pronounced after third week than the second week. Reserpine-induced behavioral depression was evident in the animals after 2 weeks, as assessed by using forced swim test. Depletion of 5-HT, dopamine and metabolites was also observed in the brain samples. Results from the present study suggest that repeated administration of reserpine could be serve as a progressive model of depression and could be used as a convenient and economic animal model for the face validity of anxiolytic compounds. Findings have potential implications with reference to the understanding and the management of treatment-resistant depression

Neurochemical and behavioral effects of green tea [Camellia sinensis] as observed in animals exposed to restraint stress

Clinical studies on psychiatric patients suggest that life events stress precipitates depression. The possible involvement of 5-Hydroxy tryptamine [5-HT; Serotonin] in depression and other behavioral deficits is also suggested by clinical studies. As a natural stimulant, green tea [Camellia Sinensis] diminishes stress, worry and anxiety, allowing the brain to focus and concentrate better. Previously we have reported that beneficial effects of green tea might be associated with altered levels of 5-HT, which in turn may help in coping with stress. Present study therefore deals with monitoring the behavior and neurochemical profile of single restrained stress in animals previously administered [for 5 weeks] with green tea. Activities in light dark activity box were monitored 1hr post restraint stress. Cumulative food intake values were monitored 24hr post restraint stress. 24hr after restrained stress, rats were decapitated to collect plasma and brain samples. Brain samples were kept stored at -70[degree sign]C until neurochemical analysis by HPLC-EC. Findings illustrate that although food intake was decreased in both green tea- as well as water treated rats, stress-induced anxiogenic effects were attenuated in green tea treated rats. Tone of 5-HT was also normalized in restrained animals. Results suggest beneficial effects of green tea in coping the stressful conditions/stimuli are related to altered 5-HT metabolism

Effects of sugar rich diet on brain serotonin, hyperphagia and anxiety in animal model of both genders

Lower levels of 5-hydroxytryptamine [5-HT; serotonin] in the brain elicit sugar craving, while ingestion of sugar rich diet improves mood and alleviates anxiety. Gender differences occur not only in brain serotonin metabolism but also in a serotonin mediated functional responses. The present study was therefore designed to investigate gender related differences on the effects of long term consumption of sugar rich diet on the metabolism of serotonin in the hypothalamus and whole brain which may be relevant with the hyperphagic and anxiety reducing effects of sugar rich diet. Male and female rats were fed freely on a sugar rich diet for five weeks. Hyperphagic effects were monitored by measuring total food intake and body weights changes during the intervention. Anxiolytic effects of sugar rich diet was monitored in light-dark transition test. The results show that ingestion of sugar rich diet decreased serotonin metabolism more in female than male rats. Anxiolytic effects were elicited only in male rats. Hyperphagia was comparable in both male and female rats. Finings would help in understanding the role of sugar rich diet-induced greater decreases of serotonin in sweet craving in women during stress

Conformational analysis and geometry optimization of apomorphine as an Anti-parkinsonian agent

Apomorphine, a dopamine D[1]/D[2] agonist, is an important drug of choice for the treatment of Parkinson's and related disorders. The present study was designed to perform the conformational analysis and geometry optimization of apomorphine. Resultant optimized structure corresponds to a substance as it is found in nature. This could be used for a variety of experimental and theoretical investigations especially in the field of pharmacokinetics. The results indicate that the best conformation of the molecule is present at minimum potential energy -88702.9595 kcal/mol. At this point molecule will be more active as histamine H[1] receptor agonist

Behavioral deficits in rats following acute administration of glimepiride: relationship with brain serotonin and dopamine

A considerable body of literature suggests that depression and diabetes mellitus are co-morbid. The present study was designed to test any possible behavioral deficits and/or neurochemical changes in the brain as induced by the anti-diabetic drugs. Twenty-four rats were divided into four groups: [i] saline [ii] glimepiride [2.5mg/kg]- [iii] glimepiride [5.0mg/kg]- and [iv] glimepiride [10 mg/kg] injected animals. Behavioral activities in Skinner's box, open field and elevated plus maze were monitored 20, 35 and 45 minutes post injection respectively. Animals were decapitated 60 minutes post injection to collect brain samples. Samples were kept at -70[degree]C until neurochemical analysis by HPLC-EC. Results from the present study show decreased time spent in the open arm of the elevated plus maze [p<0.05] at all the three doses. A decrease in the HVA [Homovanillic acid] levels at all three doses [p<0.01] was also observed along with decreased 5-HT [5-Hydroxytryptamine] [p<0.05 at 5.0 and l0mg/kg] and 5-HIAA [5-Hydroxyindoleacetic acid] [p<0.05 at all three doses] levels. Since a decrease in 5-HT metabolism can induce depression-like effects, the present study therefore suggests that the occurrence of depression in diabetic patients is due to the use of glimipride. Effects of long-term administration of smaller doses of glimipride are to be explored further to monitor tolerance in glimipride-induced deficits of serotonin. The finding may help to explore the cause of depression in diabetics for improving pharmacotherapy in diabetes

Immobilization-induced increases of systolic blood pressure and dysregulation of electrolyte balance in ethanol-treated rats

Clinical and experimental studies revealed that alcohol drinking and life event stresses are predisposing factors to hypertension. Intra and extra cellular levels of electrolytes may play important role in the pathogenesis and treatment of hypertension. Dietary intake of sodium, potassium, calcium and magnesium is suggested to have a role in the regulation of blood pressure. The present study was designed to monitor the effects of acute exposure to 2h immobilization stress and ethanol administration at a dose of 2.5g/kg body weight [i.p.] and combined effect of acute administration of ethanol and immobilization stress on systolic blood pressure [SBP], intraerythrocyte, serum and tissue electrolytes in rats. Results showed that acute exposure to 2h immobilization increased SBP, intraerythrocyte sodium and decreased intraerythrocyte potassium in water as well as in ethanol injected rats. The concentration of Na[+] and Ca[2+] increased while that of K[+] and Mg[2+] decreased in the heart and kidney tissue. Ethanol administration also increased Na[+] and Ca[2+] levelsand decreased K+ and Mg[2+] levels in the heart and kidney tissue. Restraint stress decreased serum levels of Na[+], K[+], Ca[2+], P, and Cl- and increased serum Mg[2+], glucose and haematocrit. Ethanol administration also decreased serum levels of Na[+], K[2+], Ca[2+], P, and Cl- and increased serum Mg[2+], glucose and haematocrit. The effects of ethanol and stress on the changes of blood and tissues electrolytes were additive and may be involved in the greater occurrence of hypertension in alcoholics. Our results suggested an important role of intra and extra cellular electrolytes in both stress and ethanol-induced hypertension. The findings may help to develop strategies for the treatment of hypertension in alcoholics

Apomorphine induced conditioned place preference and sensitization is greater in rats exposed to unpredictable chronic mild stress

CNS stimulants are the class of the drugs that may be used to get relief from depression. Apomorphine is a D1 and D2 receptor agonist with a CNS stimulatory effect used for the treatment of Parkinson's disease is also abused. Although many drugs of abuse produce tolerance and dependence. Long term use of pshycostimulants produce reverse tolerance described as sensitization. These drugs also have a number of other beneficial effects but their therapeutic use is limited because of abuse potential. Conditioned place preference [CPP] test is used to monitor the reinforcing effect of drugs of abuse. Stress is an important factor that precipitates and potentiates addictive effects of different drugs of abuse. The present study was designed to investigate the addictive effect of apomorphine [1mg/kg] in rats previously exposed to repeated unpredictable chronic mild stress for 10 days [animal model of depression]. Results from present study illustrate that unpredictable chronic mild stress potentiates the reinforcing effects of apomorphine as the number of entries and the time spent in the CPP compartment associated with drug administration is increased. Motor activity was taken as a parameter for behavioral sensitization which is induced by repeated administration of apomorphine, monitored as the number of cage crossings in light compartment of the CPP apparatus, also increased

Unpredictable chronic mild stress induced behavioral deficits: a comparative study in male and female rats

Stress is an important precipitant factor for depression. Changes in various body systems that occur in depression are similar to those observed in response to stress. Chronic stress may alter behavioral, neurochemical and physiological responses to drug challenges and novel stressors. Unpredictable chronic mild stress [UCMS] also produces alteration in the serotonergic [5-HT; 5-hydroxytryptamine] neurotransmission. Unpredictable chronic mild stress [UCMS] could be used as an animal model of depression. Neurochemical and behavioral effects of UCMS can be reversed by antidepressant agents, suggesting an important role of serotonin. In rodents, UCMS can elicit depression-like symptoms. The objective of the present study was to evaluate and compare the behavioral deficits induced by chronic mild stress in male and female rats and finding out the vulnerability of the two groups. Male and female rats exposed to UCMS exhibited a significant decrease in cumulative food intake as well as in growth rate. Loco motor activity in home cage and open field was also decreased. Results may contribute to our understanding of the interaction between stress and behavioral functions have to depressive disorders

Neurochemical and behavioral effects of Cinnamomi cassia [Lauraceae] bark aqueous extract in obese rats

Obesity is a risk factor leading to a number of chronic and metabolic disorders. Obesity is the fifth leading cause of global deaths. At least 2.8 million adults are dying each year as being overweight or obese. Cinnamomi cassia is widely used traditional medicinal plant, used indigenously, to decrease glucose and cholesterol. 5-Hydroxy Tryptamine [5-HT; Serotonin] is an important neurotransmitter reported to be involved in the pathophysiology of anorexia. Present study was designed to investigate the neurochemical and behavioral effects of cinnamon bark aqueous extract [CBAE] in obese rats and to find the possible involvement of 5-HT in reducing the body weight in these experimental animals. CBAE was repeatedly administered orally in the test animals for 5 weeks. A decrease in the food intake along with a concomitant increase in brain 5-HT level was observed in rats administered with CBAE. Findings may help in extending therapeutics in the pathophysiology of obesity and related eating disorders. Decrease activities in behavioral models were also monitored in CBAE treated animals.

Dose-dependent effects of tryptophan on learning and memory

The concentration of 5-hydroxytryptamine [5-HT, Serotonin] varies as a result of physiological changes in the availability of its precursor tryptophan to the serotonergic neurons in the brain. Increase in brain tryptophan occurs following an increase in plasma tryptophan concentration. Tryptophan intake increases brain serotonin metabolism and enhances memory. The Present study was designed to investigate the effects of oral administration of tryptophan [TRP] at different doses [100, 300 and 500mg/kg] for two weeks on learning and memory functions and Neurochemical changes in rats. Control rats were given drinking water. Assessment of memory in rats was done by using the water Maze, on the 14th day trail training of water Maze was given to rats and after Ih of this 2[nd] trial of these rats were done. On the next day [After 24h of trail] long-term memories of these rats were monitored. After 1 hour of this all rats were killed by decapitation using guillotine. Brain and blood was collected and stored at -70°C. Neurochemical estimations of Plasma and brain tryptophan, 5-HT and 5-HIAA in brain were made by HPLC-EC. Result showed that administration of tryptophan enhanced performance on water Maze test. Tryptophan treated animals exhibited higher level of Plasma as well as brain tryptophan. 5-HT and 5-HIAA levels were also increased in tryptophan treated rats. Findings are discussed in context with the role of 5-HT metabolism in learning and memory process in rats. Results may help to understand the 5-HT changes following long term TRP administration in a dose dependent manner and will help to suggest the use of TRP in serotonin related illnesses

Conformational analysis and geometry optimization of buspirone-A 5-HT1A receptor agonist

Buspirone, a partial 5-HTiA receptor agonist, is a clinically prescribed anxiolytic

In the present study, conformational analysis and geometry optimization of buspirone were done as per Hartree-Fock [HF] calculation method by Argus Lab 4.0.1 software

The minimum potential energy was calculated by geometry convergence function by Argus Lab software

The results indicate that the best conformation of molecule is present at minimum potential energy of-100679.5513 kcal/mol. At this point, buspirone will be more active

Neurochemical and behavioral effects of green tea [Camellia sinensis]: a model study

Being rich in polyphenolic compounds such as flavonoids, green tea is suggested to be a potential candidate for the treatment of obesity, stress, depression, Parkinson's and other disorders. Since serotonin has an important role in the pathophysiology of these disorders, present study was designed to monitor the effects of green tea in rats. Green tea extract was provided to the male Albino Wistar rats for 5 weeks, and effects on behaviors were monitored. Results show a decrease in food intake after 5th week but not before. An increase in locomotive activities of the animals was observed, as monitored in novel as well as in familiar environment. Anxiolytic effects were observed in elevated plus maze but not in light dark activity box. An increase in dopamine and serotonin turnover was observed. Our results suggest that beneficial effects of green tea drinking might be due to alteration of serotonin and/or dopamine metabolism. We thereby propose that in further experiments, green tea should be administered in animal model of learned helplessness and effects on the development of adaptation to stress should be monitored. Neurochemical estimations of catecholamine and indoleamine in these animal models of stress exposed to green tea would help in understanding the anxiolytic effects of green tea

Possible clinical application of resting-state fMRI in neuropsychiatric disorders

Functional brain imagings studies have shown brain regions having greater neural activity during an experimental task than during rest or sensory-motor task with reduced cognitive demand. Based upon this hypothesis that supports the idea of [default mode of brain function] recent studies have focused on brain regions in which neuronal activity is greater during resting-state than during an experimental task with cognitive demand. Recent Studies have showed that resting-state connectivity is crucial for cognitive performance. To detect dysfunctional connectivity and activity in various resting-state networks in brain that has been suggested to be underlying pathophysiology of some neuropsychiatric disorders, resting-state fMRI could be considered as a relatively novel and beneficial tool for diagnosis of these disorders. In this article, brain resting-state networks are briefly introduced for better understanding of possible clinical applications of resting-state fMRI in diagnosis and early detection of some neuropsychiatric diseases that have been studied in recent years

Regional neurochemical profile following development of apomorphine-induced reinforcement

Dopamine is primary neurotransmitter which mediates the reinforcing effects of abused drugs, serotonin [5- Hydroxytryptamine; 5-HT] also has a crucial role in the pathophysiology of addiction. The binding sites of various drugs of abuse are different from each other, their final rewarding effects are mediated by an increase in the dopamine level in the Nucleus Accumbens. The present study used conditioned place preference [CPP] test to monitor apomorphine's reinforcing effects. Associated alterations in 5-HT and dopamine metabolism were also monitored in various brain regions by HPLC-EC. Withdrawal from apomorphine administration [at a dose of 1.0 mg/kg on six alternate days] induced reinforcement as monitored in the conditioned place preference [CPP] paradigm. Serotonin and dopamine metabolism was also changed particularly in the ventral and dorsal striatum. Results therefore suggest desensitization of dopamine receptors in the presynaptic site is involved in apomorphine-induced reinforcement. Desensitization of somatodendritic 5-HT[1A] receptors resulting in increased availability of 5-HT at 5-HT[2C] receptors could attenuate apomorphine-induced reinforcement. Therefore, further investigations in this area should focus on attempts to attenuate apomorphine-induced reinforcement by desensitizing somatodendritic 5-HT[1A] receptors

Effects of apomorphine on locomotive activity and monoamine metabolism: a dose related study

We have monitored dose dependent effects of apomorphine on motor activity and monoamine metabolism. Behavioral sensitization and craving, which develop upon repeated treatment with dopamine receptor agonist apomorphine, are major limitations of the therapeutic use of apomorphine in Parkinson's patients. Effects of single [intraperitoneal] injection of apomorphine at different doses [i.e., 1.0, 2.0 and 4.0 mg/kg] on exploration in a novel environment [open field] and locomotion in a familiar environment [home cage] were investigated. Results show significantly enhanced activity in home cage [monitored 5min post injection] in a dose dependent manner. However, no significant influence of apomorphine on exploration of open field was observed in the present study [monitored 15min and 40min post injection]. Animals were decapitated 1 hr post apomorphine injection and whole brains of animals were collected and stored at -70°C. Biogenic amines [i.e., 5-Hydroxytryptamine and dopamine] and metabolites [i.e., Dihydroxyphenylacetic acid, Homovanillic acid and 5-Hydroxyindoleacetic acid] were estimated by reverse phase High Performance Liquid Chromatography with electrochemical detector [HPLC-EC]. Effect of low [l.0mg/kg] dose of apomorphine was found to be nonsignificant on 5-Hydroxytryptamine [5-HT], 5-Hydroxyindoleacetic acid [5-HIAA] and dopamine [DA] levels. Moderate [2.0 mg/kg] dose of drug increased [p<0.05] levels of Homovanillic acid [HVA]. Whereas, high [4.0 mg/kg] dose of apomorphine decreased Dihydroxyphenylacetic acid [DOPAC] levels. Results could be helpful in elucidating the effect of apomorphine at different doses and its implication for extending therapeutics in Parkinson's and related disorders

Neurochemical and behavioral effects of M-CPP in a rat model of tardive dyskinesia

Present study was designed to monitor the responsiveness of 5HT [5-Hydroxytryptamine] -2C receptors following the long-term administration of haloperidol in rats. Effects of m-CPP [meta-Chlorophenyl piperazine] were monitored 48h after withdrawal from repeated [twice a day for 5 week] administration of haloperidol [at the dose of 1mg/kg]. Vacuous chewing movements [VCMs] were monitored on weekly basis. Two days after withdrawal, animals were injected with saline [1ml/kg of body weight] or m-CPP [3mr/kg of body weight]. Activities in open field and light dark activity box were monitored 15 and 30 min post injection respectively. Animals were then decapitated [4h post injection] to collect dorsal striatum [DS] samples for the neurochemical analysis by HPLC-EC [High performance Liquid Chromatography with Electrochemical detection] method. Results from the present study showed significant hypolocomotive effect of m-CPP [p<0.05] in both repeated haloperidol as well as repeated saline injected rats. Neurochemical analysis of DS by HPLC-EC method showed that administration of m-CPP significantly [p<0.05] decreased 5-HIAA [5-Hydroxyindol acetic acid] in repeated haloperidol injected rats. In conclusion, present study provides evidence that 5HT-2C receptors become hypersensitive in a rat model of Tardive Dyskinesia [TD]. These findings have potential implication in the treatment of TD and attenuation of EPS induced by typical neuroleptics