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

Protective effects of rice bran oil in haloperidol-induced tardive dyskinesia and serotonergic responses in rats

Effect of administration of Rice bran oil [RBO] was evaluated on haloperidol elicited tardive dyskinesia in rats. Albino Wistar rats treated with haloperidol in drinking water at a dose of 0.2mg/kg/day and RBO by oral tubes at a dose of 0.4 mL/day for 5 weeks. Motor coordination, VCMs and 8-hydroxy-2-[di-n-propylamino] tetraline][8-OHDPAT] _syndrome were monitored. Striatal serotonin [5-hydroxytryptamine; 5-HT] and 5-hydroxyindolacetic acid [5- HIAA] levels were determined by high performance liquid chromatography [HPLC-EC]. Rats treated with haloperidol orally at a dose of for a period of 5 weeks developed VCMs, which increased progressively as the treatment continued for 5 weeks. Motor coordination impairment started after the 1[st] week and was maximally impaired after 3 weeks and gradually returned to the 1[st] week value. Co-administration of RBO prevented haloperidol_induced VCMs as well impairment of motor coordination. The intensity of 8-OH-DPAT_induced syndrome and decreased 5-HT metabolism were greater in water + haloperidol treated animals than RBO + haloperidol treated animals. The present study suggested that involvement of free radical in the development of TD and point to RBO as a possible therapeutic option to treat this hyperkinetic motor disorder

Co-treatment with imipramine averted haloperidol-instigated tardive dyskinesia: association with serotonin in brain regions

Outcome of imipramine [IMI] treatment was scrutinized on progression of haloperidol instigated tardive dyskinesia [TD]. 0.2 mg/kg/rat dosage of haloperidol provided orally to rats for 2 weeks enhanced vacuous chewing movements that escalated when the process proceeded for 5 weeks. Following 2 weeks co-injection 5 mg/kg dosage of IMI was diminished haloperidol-instigated VCMs and fully averted following five weeks. The potency of 8-OH-DPATinstigated locomotor activity exhibited higher in saline+haloperidol treated rats while not observed in IMI+ haloperidol treated rats. 8-OH-DPAT-instigated low 5-hydroxytryptamine [5-HT; serotonin] metabolism was higher in saline+ haloperidol treated rats when compare to IMI+ haloperidol treated rats in both regions of brain [striatum and midbrain]. It is recommended that IMI possibly competent in averting TD, in cases receiving treatment to antipsychotics

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 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

Altered brain serotonergic neurotransmission following caffeine withdrawal produces behavioral deficits in rats

Caffeine administration has been shown to enhance performance and memory in rodents and humans while its withdrawal on the other hand produces neurobehavioral deficits which are thought to be mediated by alterations in monoamines neurotransmission. A role of decreased brain 5-HT [5-hydroxytryptamine, serotonin] levels has been implicated in impaired cognitive performance and depression. Memory functions of rats were assessed by Water Maze [WM] and immobility time by Forced Swim Test [FST]. The results of this study showed that repeated caffeine administration for 6 days at 30 mg/kg dose significantly increases brain 5-HT [p<0.05] and 5-HIAA [p<0.05] levels and its withdrawal significantly [p<0.05] decreased brain 5-HT levels. A significant decrease in latency time was exhibited by rats in the WM repeatedly injected with caffeine. Withdrawal of caffeine however produced memory deficits and significantly increases the immobility time of rats in FST. The results of this study are linked with caffeine induced alterations in serotonergic neurotransmission and its role in memory and depression

Behavioral and neurochemical profile of some novel phenacyl based isonipecotamide derivatives

Study of natural products led to the development of new molecules of potential biological activity. Piperidine nucleus constitutes one of the components of various alkaloids and drugs. During the course of our project regarding the synthesis of derivatives of piperidine carboxamide to study the effects of these compounds as anti-depressive agents, some of the compounds exhibited significant effects at all three doses, through open field activity thus establishing a direct relationship between dose and locomotion. Moreover, these compounds have also shown the decreased level of 5-HT alone with increased level of dopamine as an indication of their antagonism towards 5-HT receptor

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

Attenuation of somatodendritic responses to 8-hydroxy-2-di-n-propylamino tetralin following long-term dietary sugar consumption in rats

To determine changes in response to a selective serotonin-1 A receptor agonist 8-hydroxy-2-[di-n-propylamino] tetralin [8-OH-DPAT] following long-term consumption of sugar as part of meal in rats. Experimental study. The Department of Biochemistry, University of Karachi, from June to August 2005. The study was conducted on 24 male albino Wistar rats. Sugar containing diet was prepared by mixing standard rodent diet and table sugar in the ratio of 3:1 [w/w] and rats were fed freely on this diet. Control rats were fed freely on standard rodent diet. After five weeks of treatment, control and sugar diet treated animals were injected with 8-OH-DPAT, at a dose of 0.5 mg/ml/kg, to monitor the effects of drug on food intake and brain serotonin [5-hydroxytryptamine, 5-HT] metabolism. Dissected neural tissue was analyzed electrochemically and findings were compared by Newman-Keuls test. Administration of 8-OH-DPAT elicited hyperphagia and decreased 5-HT metabolism in normal diet treated rats. The neurochemical and hyperphagic responses to 8-OH-DPAT were smaller in sugar than normal diet treated animals suggesting a downregulation of somatodendritic responses in sugar diet treated animals. A decrease in serotonin metabolism but not an increase in the responsiveness of somatodendritic 5-HT-1A receptors is involved in sugar-rich diet induced hyperphagia

Dietary supplementations of amino acids: evidence for enhanced serotonergic functions following haloperidol withdrawal in rat medial prefrontal cortex

To investigate the effects of orally supplemented amino acids L-Tryptophan [Trp] and L-Valine [Val] in rats repeatedly injected with haloperidol following one week of drug withdrawal, with particular reference to extrapyramidal symptoms [EPS] and serotonin [5-hydroxytryptamine; 5-HT] metabolism in medial prefrontal cortex [mPFC]. Experimental study. Place and Duration of Study: Department of Biochemistry, University of Karachi from December 2007 to February 2008. The study was conducted on thirty six locally bred male Albino Wistar rats. Freshly prepared amino acids [Val and Trp] were added in the drinking water of rats on alternate days and haloperidol at doses of 5.0 mg/kg or saline were injected twice daily for three weeks following one week of withdrawal. Locomotor/ exploratory activities were scored in activity boxes and open field apparatuses. Catalepsy was monitored on an inclined surface. The animals tested for locomotor activity and catalepsy for two weeks follow-up post-injections plus one week of drug withdrawal were decapitated to collect mPFC regions of rat brain for neurochemical analysis by high performance liquid chromatography with electrochemical detection [HPLC-EC]. There was significant increase [p < 0.01] in locomotor activity in rats orally supplemented with Val and Trp following one week of drug withdrawal from repeated administration. Marked reduction in cataleptogenic effects of the drug was also observed. Significant [p < 0.01] increases in the brain Trp and mPFC 5-HT metabolism in Val and Trp supplemented animals were also noticed. These findings help to demonstrate the effect of dietary amino acids, in particular, Trp to potentiate mPFC serotonergic modulation of neuroleptic activity

Repeated administration of Nigella sativa decreases 5-HT turnover and Nigella produces anxiolytic effects in rats

The black cumin or Nigella sativa L. seeds have many acclaimed medicinal properties. Pharmacological studies have been conducted on the aqueous and methanol extracts of N. sativa L. seeds to evaluate their effects on the central nervous system. In the present study, N. sativa oil was used to study its effect on anxiety in rats. Open field and elevated plus maze models were selected for the evaluation of anxiolytic effect of drug. After four weeks of daily administration of drug, the rats exhibited an increase in open field activity. The drug also produced anti-anxiety effect in rats when tested in elevated plus maze. Concentrations of 5-HT, 5-HIAA in brain and concentrations of plasma and brain tryptophan determined by HPLC-EC detector. Result shows that oral administration of N. sativa oil increased brain levels of 5-HT but the levels of brain 5-HIAA decreased significantly. Brain and plasma levels of tryptophan also increased significantly following oral repeated administration of N. sitiva oil. Based on this, it may be suggested that N. sativa oil is a useful choice for the treatment of anxiety

Serotonin-1A receptor responsiveness in stress and following adaptation to stress

Stress is one of the environmental factors that may predispose psychiatric illness such as, depression. Stress may come from external environment in the form of stimuli such as heat, cold, loud noise and lack of oxygen. A deficiency of serotonin [5-hydroxytryptamine; 5-HT] is described in human depression. Parallel studies on experimental animals show that exposure to an uncontrollable stress inducing situation elicits behavioral deficits and increases serotonin metabolism in the brain. Stress-induced behavioral deficits and the increases of brain serotonin did not occur when the stress was administered repeatedly for 5 days, suggesting adaptation has occurred. The present study shows that responses to 8-hydroxy-2-[di-n-propylamino]tetraline [8-OH-DPAT], a selective 5-HT 1A agonist decreased following exposure to single stress and the decreases were normalized following adaptation to stress. The drug 8-OH-DPAT was also found to attenuate stress-induced behavioral deficits. The results are discussed in the context of stress-induced psychiatric disorder such as, depression and its treatment by 5-HT 1A agonist

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

Effects of long term consumption of sugar as part of meal on serotonin 1: a receptor dependent responses

In view of an effect of high intake of sugar on brain serotonin [5-hydroxytryptamine, 5-HT] and a role of serotonin in the regulation of appetite, the present study concerns pre and postsynaptic responses to a selective 5-HT-1A receptor agonist 8-hydroxy-2-[di-n-propylamino] tetralin [8-OH-DPAT] following long term consumption of sugar as part of meal in rats. Sugar diet was prepared by mixing standard rodent diet and table sugar in ratio of 3:1 [w/w] and rats were fed freely on this diet for five weeks. Control rats were fed freely on standard rodent diet. After five weeks 8-OH-DPAT at a dose of 0.5mg/kg/ml was injected to both the groups to compare effectiveness of the drug to elicit hyperphagia [presynaptic response] and elicited hyperactivity syndrome [postsynaptic response]. Results showed that 8-OH-DPAT-induced forepaw treading and flatbody posture were smaller in sugar than normal diet treated rats. Conversely 8-OH-DPAT-induced hyperlocomotion was greater in sugar than normal diet treated rats. 4h Food consumption was greater in sugar than normal diet treated rats while 8-OH-DPAT-induced hyperphagia significant in normal diet treated rats was not observed in sugar diet treated rats. The results show a decrease in the effectiveness of pre as well as postsynaptic 5-HT-1A receptor dependent responses following long term consumption of sugar diet. Role of serotonin receptor responsiveness on mood and impaired adaptation to stress is discussed

5-HT-1A receptor responsiveness following subchronic administration of buspirone

Anxiety and its disorders have long been known to be familial. Anxiety levels are associated with low social connectedness and high environmental threats. Studies provide evidence that anxiety disorders may be link to malfunctioning of serotonin neurotransmission. The present study is designed to monitor serotonin-1A [5-HT-1A] receptor responsiveness following subchronic administration of a serotonergic anxiolytic buspirone. Administration of 8-hydroxy-2-[di-n-propylamino]-tetralin [8-OH-DPAT] at a dose of 0.25 mg/kg produced comparable syndrome in repeated saline and repeated buspirone injected rats. Cage crossings were significantly lower in repeatedly buspirone injected rats. Decreases in 5-hydroxytryptamine [5-HT] and 5- hydroxyindoleacetic acid [5-HIAA] levels were higher in saline than buspirone injected rats. Result suggests that following long term administration of buspirone somatodendritic and postsynaptic 5-HT-1A receptors are desensitized. Role of serotonin 1 A receptors in the treatment of anxiety is discussed