Nootropic and hypophagic effects following long term intake of almonds (Prunus amygdalus) in rats.

INTRODUCTION: Over a period of time researchers have become more interested in finding out the potential of various foods to maintain the general health and to treat diseases. Almonds are a very good source of many nutrients which may help to sharpen the memory and to reduce cardiovascular risk factors. OBJECTIVE: The present study was conducted to evaluate the nootropic effects of almonds. Effect of oral intake of almond was also monitored on food intake and plasma cholesterol levels. METHODS: Rats were given almond paste orally with the help of feeding tube for 28 days. Memory function in rats was assessed by Elevated Plus Maze (EPM) and Radial Arm Maze (RAM). Brain tryptophan, 5-HT and 5-HIAA were estimated at the end of the treatment by HPLC-EC method. RESULTS: A significant improvement in learning and memory of almond treated rats compared to controls was observed. Almond treated rats also exhibited a significant decrease in food intake and plasma cholesterol levels while the change in growth rate (in terms of percentage) remained comparable between the two groups. Analysis of brain tryptophan (TRP) monoamines exhibited enhanced TRP levels and serotonergic turnover in rat brain following oral intake of almonds. CONCLUSION: The findings show that almonds possess significant hypophagic and nootropic effects. Results are discussed in context of enhanced 5-HT metabolism following almond administration.

Tolerance in the anxiolytic profile following repeated administration of diazepam but not buspirone is associated with a decrease in the responsiveness of postsynaptic 5-HT-1A receptors.

To understand the role of serotonin (5-hydroxytryptamine; 5-HT)-1A receptors in the treatment of anxiety and the development of tolerance to benzodiazepines the present study was designed to monitor the responsiveness of postsynaptic 5-HT-1A receptors following repeated administration of diazepam and buspirone. Results show that tolerance in the anxiolytic profile is produced following repeated administration (2 weeks) of diazepam (2 mg/kg) but not buspirone (0.5 mg/kg). The behavioral effects of 8-OH-DPAT at a dose of 0.25 mg/kg were monitored 3 days after repeated administration of saline or buspirone or diazepam. The results show that 8-OH-DPAT elicited forepaw treading was smaller in repeated diazepam but not repeated buspirone injected rats, while hyperlocomotive effects of 8-OH-DPAT were smaller in both repeated buspirone and repeated diazepam injected rats. The results suggest that postsynaptic 5-HT-1A receptor-dependent responses were attenuated following long-term administration of diazepam but not buspirone. Role of 5-HT-1A receptors in the development of tolerance to the anxiolytic effects of diazepam but not buspirone is discussed.

Long-term tryptophan administration enhances cognitive performance and increases 5HT metabolism in the hippocampus of female rats.

It has been shown in various studies that increase in serotonergic neurotransmission is associated with increased memory consolidation whereas low brain 5HT impairs memory performance. In the first phase of our study we found that tryptophan (TRP) administration for 6 weeks increased plasma TRP and whole brain TRP, 5HT and 5HIAA levels. Many brain regions are involved in the learning process but particularly the hippocampus is known to have key role in learning and memory. The present study was therefore designed to investigate the effects of TRP loading particularly on hippocampal 5HT metabolism and cognitive performance in rats. TRP-treated rats demonstrated spatial enhancement as evidenced by a significant decrease in time to find the hidden food reward in radial arm maze test (RAM). The important finding of the present study was the greater increase in the 5HT metabolism in hippocampus than in any other brain region of the TRP-treated rats. This increased 5HT metabolism in the hippocampus emphasizes the involvement of this region in memory process.

Behavioral effects of 8-OH-DPAT in single and repeated haloperidol injected rats.

Haloperidol is an antipsychotic drug and shown to be antagonist at D2 receptors and found to cause severe impairment of locomotor performance. The serotonin (5HT1A) receptor agonist 8-OH-DPAT has been reported to attenuate extrapyramidal side effects of haloperidol. The present study was designed to examine the modulatory effect of serotonergic activities on haloperidol induced up-regulation of dopamine D2 receptors. In the acute phase of study, 8-OH-DPAT (0.5 mg/kg/ml) elicited behavioral syndrome was monitored in rats preinjected with haloperidol(5 mg/kg/ml). Results of single haloperidol administration revealed that 8-OH-DPAT induced forepaw treading (p < 0.05) and hyperlocomotion (p < 0.01) were smaller in haloperidol than saline preinjected rats. In repeated phase of study, 8-OH-DPAT (0.5 mg/kg/ml) induced behavioral syndrome was monitored in rats injected with haloperidol for 10 days (x2). The result of repeated haloperidol administration showed that 8-OH-DPAT elicited flat body posture (p < 0.01) was greater in repeated haloperidol injected rats than repeatedly saline injected rats. Relationship between 5HT1A receptors and D2 receptors has been discussed. It is suggested that combining neuroleptics with 5HT1A ligands is thought to improve the preclinical profile of neuroleptics and may be of interest in the development of new compounds that have greater therapeutic potential and/or better tolerated.

Decreases of brain serotonin following a food restriction schedule of 4 weeks in male and female rats.

Male and female rats fed on a restricted feeding (RF) schedule of 4 weeks to produce 20-25% reduction in body weight, were killed before (starved) and after (fed) the presentation of food to compare 5-hydroxytryptamine (5-HT) metabolism in the hypothalamus with respective freely feeding (FF) controls and to monitor sex differences in RF-induced changes of 5-HT. RF decreased plasma tryptophan concentration in RF starved and RF fed females and also in RF starved males. In the hypothalamus tryptophan levels decreased in RF starved and RF fed female rats and RF fed males. 5-HT decreased in both RF starved and RF fed male and female rats and the decreases were comparable in the two sexes. 5-hydroxyindoleacetic acid (5-HIAA), a major metabolite of 5-HT was not affected. Food restriction decreased 5-HT concentration in the rest of the brain of male but not female rats. Possible implications of the findings in the pathogenesis of food restriction/starvation related disease anorexia nervosa and its greater occurrence in women than men is discussed.

Neurochemical and extra pyramidal effects of atypical neuroleptic clozapine in rats.

In view of a possible role of serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) in neuroleptic-induced muscle rigidity and catalepsy, the present study is designed to investigate the neurochemical and extrapyramidal effects of atypical antipsychotic/neuroleptic drug i.e., Clozapine (CZP) on the metabolism of serotonin and dopamine particularly in the caudate (a region of the brain involved in the control of movement), accumbens and rest of the rat brain. Interaperitoneal (i.p) injections of CZP at doses of 5.0 & 10 mg/kg decreased significantly (p<0.01) locomotor activity in familiar (home cage) environment. CZP produced a significant (P<0.01) cataleptic response only at doses of 10 mg/kg used. Maximal cataleptic effects in rats occurred at high doses of CZP. Acute administration of CZP significantly (p<0.01) decreased levels of NA in accumbens at all the doses used. Significant increases (p<0.01) in the levels of NA observed in rest of the brain only at moderate dose (5 mg/kg) of CZP. Results showed significant (p<0.01) increases in the levels of caudate DA following the administration of CZP at 10 mg/kg. However administration of CZP at all the doses produced similar significant (p<0.01) increases in the levels of HVA in all the regions of the rat brain. Overall insignificant effects of CZP occurred on brain regional TRP. However, plasma TRP significantly (p<0.01) increased at 2.5 mg/kg dose of CZP. Administration of CZP at doses of 2.5 and 10 mg/kg significantly (p<0.01) decreased 5-HT levels in the rest of the brain. Administration of CZP produced insignificant (p>0.05) effects on 5-HIAA levels in the caudate and accumbens regions but CZP at doses of 2.5 and 5 mg/kg significantly (p<0.01) decreased 5-HIAA levels in the rest of the brain. Neurochemical and extrapyramidal effects of atypical antipsychotic (clozapine) are discussed in relation to a potential therapeutic profile in rats.

Attenuation of 8-OH-DPAT-induced decreases in 5-Ht synthesis in brain regions of rats adapted to a repeated stress schedule.

Previously it has been shown that single episode of 2 h restraint produced behavioral deficits in rats which were not observed following daily restraint period of 2h/day for 5 days. It was suggested that adaptation to a stress schedule develops when the similar stress is administered repeatedly. In view of a role of 5-hydroxytryptamine (5-HT) in adaptation to stress the present study concerns effects of a 5-HT-1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on the synthesis of 5-HT in brain regions of rats adapted to a repeated restraint stress schedule of 2h/day for 5 days. The drug injected systemically at a dose of 1 mg/kg decreased 5-HT synthesis in the hypothalamus, cortex, hippocampus, striatum and raphe regions of previously unrestrained rats. These decreases were either smaller (raphe) or not observed (hypothalamus, cortex and hippocampus) in most brain regions of rats adapted to the repeated restraint stress schedule of 2h/day for 5 days. These results suggest that a subsensitive negative feedback effect on the synthesis of 5-HT leading to an increase in synaptic 5-HT concentration might help coping with stress demand to produce adaptation to stress.

Increased precursor availability did not increase food intake and 5-HT turnover rate in the hypothalamus of diazepam injected rats.

In view of a possible role of serotonin (5-hydroxytryptamine; 5- HT) in regulation of appetite and anxiety, the effects of 1, 3 and 5 mg/kg doses of diazepam on brain serotonin precursor and effects of single and repeated diazepam (1 mg/kg 2* daily for 4 days) administration on hypothalamic 5-HT, 5-hydroxyindoleacetic acid (5-HIAA and 5-HIAA/5-HT ratio are investigated in rats. Daily diazepam treatment decreased food intakes. Diazepam injected rats exhibited a dose-dependent increase of tryptophan in the hypothalamus. Administration of diazepam (1 mg/kg) to 4 day saline injected rats on the 5th day increased 5-HT and decreased 5-HIAA levels in the hypothalamus. 5-HIAA/5-HT level also decreased. 4-day diazepam injected rats injected with saline on the 5th day also exhibited similar changes of 5-HT. 5-HIAA and 5-HIAA/5-HT ratio. Administration of diazepam to 4 day diazepam injected rats again decreased 5-HIAA concentrations but did not increase 5-HT levels in the hypothalami of rats. Possible mechanism involved in the anorectic effects of diazepam-induced changes of hypothalamic 5-HT turnover rate is discussed.

A study on the effects of some new derivatives of piperidine on neurotransmitters.

Four chemically synthesized derivatives of piperidine were subjected to evaluate their pharmacological actions on Nervous System in male albino mice. The effects on neuro-transmitters such as catecholamine and indolamine assuming that these derivatives might alter them differently, studied by HPLC-EC method. The result revealed that brain dopamine and catecholamine were altered by most of these derivatives at the doses of 100 mg/kg body weight.

Inhibition of restraint-induced anorexia by injected tryptophan.

Tryptophan injected at doses of 50mg/kg did not alter 24 h cumulative food intake and growth rate in rats. A single episode of 2 h restraint stress decreased food intake and growth rate of saline and tryptophan injected rats. The decreases of both food intake and growth rate were smaller in tryptophan injected (food intake 23.9% p<0.05; growth rate 2.9% p<0.05) than saline injected (food intake 78.5% p<0.01; growth rate 6.1% p<0.01) rats suggesting that tryptophan administration inhibits restraint-induced anorexia. Following an acute challenge with 2h restraint increases of 5-hydroxytryptamine (5-HT; serotonin) and 5-hydroxyindoleacetic acid (5-HIAA) but not tryptophan were greater in tryptophan injected than saline injected rats. The findings imply that tryptophan-induced increases of brain 5-HT and 5-HIAA have little effect on functional serotoninergic activity under basal conditions but a facilitatory effect on functional response occurs in conditions of increased serotoninergic neuronal activity such as during stress.

The neurochemical profile of long term oral administration of moclobemide.

Moclobemide, a benzamide derivative, predominantly inhibits the A form of monoamine oxidase (MAO) and its MAO binding is reversible. Acute administration of moclobemide has been shown to induce an increase in brain levels of monoamines and a concomitant decrease in their respective metabolite. In the present study, the drug was administered to rats orally in drinking water at doses of 0.5-1.0 mg/day/rat of an average weight of 250 g for three weeks. This was equivalent to the recommended human dose of 150-300 mg/day. The drug administration did not alter food intake, growth rate and activity of rats. Brain levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) increased. However, increases in 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) as reported in acute studies were not observed following chronic drug administration in the present study in addition, an increase in brain levels of tryptophan also occurred. Neurochemical profile of long-term moclobemide administration is explainable in terms of an inhibition of MAO activity, increased availability of 5-HT precursor tryptophan and decreased egress of monoamine metabolites.

Effect of chlorpromazine on brain biogenic amines in normal and hyperglycemic state.

In present study the effects of chlorpromazine (CPZ) were studied on NA, DA and its metabolities i.e. DOPAC and HVA as well as on 5-HT and its metabolite 5-HIAA in normal and hyperglycemic rats. Significant differences were noted in brain biogenic amines of normal and diabetic control animals. In case of CPZ treated normal and hyperglycemic rats significant differences were observed only in case DOPAC and 5-HIAA. NA and 5-HIAA levels were significantly affected by CPZ and diabetes interaction.

Neurochemical and behavioural effects of long term intake of tea.

Tea consumption in many cases is the main source of caffeine intake in humans. In the present study neurochemical and behavioural effects of long-term tea intake are monitored in rats. Long-term tea administration did not alter plasma tryptophan (TRP) but significantly attenuated brain TRP and 5-hydroxytryptamine (5-HT, serotonin) levels. Brain 5-hydroxyindole acetic acid (5-HIAA) was comparable in both tea-treated and control rats. An increase in home cage activity was observed after one week in rats taking tea as sole source of liquid, whereas no change on the activity was observed in an open field. Caffeinism has been associated with depression. The decreases of brain monoamine metabolism observed in present study are discussed as lowering of mood observed in tea or coffee consumers.

Effects of diazepam and cinchocaine on biogenic amines.

Neurochemical and behavioural research show that benzodiazepines are well know anxiolytic drugs, which are also used for the treatment of epilepsy, hypnosis and insomnia. Administration of benzodiazepine to experimental animals produces anxiolytic-like effects in various animal and decreases exploratory activity. Psychomotor stimulants such as cinchocaine also showed potent effect on brain biogenic amines and their metabolite. The present studies indicate the changes in dopamine and 5-HT and their metabolites levels after acute administration of cinchocaine and diazepam.

Neurochemical and behavioural effects of diazepam: evidences from animal models.

Neurochemical and behavioural research show that benzodiazepines (BZs) are the well-known anxiolytic drugs which are also used for the treatment of epilepsy, hypnosis and insomnia. Administration of BZs to experimental animals produces anxiolytic-like effects in various animal models and decreases exploratory activity. A role of serotonin (5-HT; 5-hydroxytryptamine) in both anxiolytic and anti-exploratory effects of BZs have been suggested. Drugs which mimic 5-HT function at the post synaptic sites have been shown to decrease anxiety in experimental animals. The present study analyses regionally specific effects of BZs on brain serotonin metabolism in relation to the reported behavioural and therapeutic profiles of the drugs.

Effects of cinchocaine cocaine analogs on brain mono amines and their metabolites in male mice.

Cinchocaine analogs were studied to determine the effects of acute administration of cocaine analogs on dopamine, 5- hydroxytryptamine (5-HT) and their metabolites. Psychomotor stimulants, (such as cinchocaine), potently influencing dopamine transport carrier were used to characterize in-vivo DA transmission. DA, DOPAC, HVA level and indoleamine were measured in brain after drug administration. Significant changes in levels of DA, DOPAC, 5-HT, 5HIAA and HVA were noted. The present findings suggests that acute administration of cinchocaine increases the level of Dopamine, 5-HT and their metabolites and alter the level of amines as compare to control group. These studies also indicate that difference in structure do not affect the binding sites and inhibition of amine uptake.

Adaptation to repeated restraint stress in rats: failure of ethanol-treated rats to adapt in the stress schedule.

Adaptation to a repeated restraint stress schedule was monitored in ethanol-treated and control rats. A single episode of 2 h restraint decreased food intake in both control and ethanol-treated rats. The decreases in control rats were not observed following the 5th daily restraint of 2 h/day, suggesting that adaptation has occurred. Ethanol-treated rats, however, exhibited decreased food intake even after 5th daily restraint of 2 h/day. Ethanol administration decreased weekly but not daily cumulative food intake in unrestrained rats. Food intakes of ethanol-treated and control restrained rats were comparable following 1st-3rd daily restraints, but were smaller in ethanol-treated rats following the 4th and 5th daily restraints. Open-field ambulatory activities monitored 24 h after the 5th daily restraint on the 6th day were comparable in control restrained and unrestrained rats. Ethanol-treated and control unrestrained rats also exhibited comparable ambulation, but ethanol-treated rats exhibited smaller activity than control restrained or ethanol-treated unrestrained rats. Fluid intakes of ethanol and control rats were comparable during the 2 weeks of ethanol administration, but daily restraint schedule decreased ethanol intake. The findings show adaptation to repeated restraint in control rats and inability of ethanol-treated rats to adapt in the stress schedule. These findings imply that excessive alcohol consumption may impair adaptation to stress and thus conceivably precipitate depression.

Food restriction decreases serotonin and its synthesis rate in the hypothalamus.

Rats fed on a restricted feeding (RF) schedule of 4 h day-1 to produce a 15-20% reduction in body weight were killed before (starved) and after (fed) the presentation of food on the sixth day to compare 5-hydroxytryptamine (5-HT; serotonin) metabolism and synthesis rate in the hypothalamus with freely feeding (FF) controls. The RF rats showed lower 5-HT concentration and synthesis rate than FF controls. Restricted feeding did not decrease tryptophan concentration in the hypothalamus. However, RF-fed rats had lower tryptophan concentration than RF starved rats. 5-HIAA concentration was comparable in RF fed rats and FF controls but higher in RF starved rats. Possible implications of the findings in the pathogenesis of the food deprivation/starvation-related disease anorexia nervosa are discussed.

Regionally specific effects of diazepam on brain serotonin metabolism in rats: sustained effects following repeated administration.

The effects of single (1mg/kg) and repeated (1mg/kg 2* daily for 4 days) diazepam administration are investigated on brain regional 5-hydroxytryptamine (5-HT; serotonin) and 5-hydroxy indoleacetic acid (5-HIAA) concentration in rats. Daily treatment decreased food intakes but body weights did not decrease. Administration of diazepam (1mg/kg) to 4 day saline injected rats on the 5th day decreased 5-HT levels in the hippocampus and increased it in the hypothalamus. 5-HIAA levels were increased in the striatum and decreased in the hypothalamus 4 day diazepam injected rats injected with saline on the 5th day also exhibited similar changes of 5-HT and 5-HIAA. Cortical levels of 5-HIAA were also smaller in these rats. Administration of diazepam to 4 day diazepam injected rats again decreased 5-HT in the hippocampus and 5-HIAA in the hypothalamus. 5-HT and 5-HIAA were both decreased in the striatum. Regionally specific effects of diazepam on brain serotonin metabolism are discussed in relation to their possible functions.

Stress and hypertension: role of serum, red cell and tissue electrolytes.

The role of stress in the precipitation of hypertension is often described in clinical studies, although the underlying mechanism remains unknown. The present study concerns the role of electrolytes in stress induced hypertension in rats. Acute immobilization stress of one hour elevated systolic blood pressure (SBP) in rats. Restraint induced blood pressure elevation was associated with increased sodium concentration in the red cells, heart and kidney, and decreased potassium in the red cells. Magnesium concentration increased and calcium concentration decreased in the serum. Increases of calcium and decreases of magnesium were also observed in the heart and kidney tissues. The results may help toward an understanding of the relationship between hypertension and electrolyte homeostasis. A possible role of Na(+)-K(+)-ATPase activity leading to observed changes of electrolytes or vice versa is discussed.