Attenuation of cadmium-induced decline in spatial, habituation and recognition memory by long-term administration of almond and walnut supplementation: role of cholinergic function

Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity. Cadmium was administered at the dose of 50 mg/kg/week. Whereas, almond and walnut was supplemented at the dose of 400 mg/kg/day along with cadmium administration to separate set of rats. At the end of experiment, memory function was assessed by Morris water maze, open field test and novel object recognition test. Results of the present study showed that cadmium administration significantly reduced memory retention. Reduced acetylcholine levels and elevated acetyl cholinesterase activity were also observed in frontal cortex and hippocampus of cadmium treated rats. Malondialdehyde levels were also significantly increased following the administration of cadmium. Daily supplementation of almond and walnut for 28 days significantly attenuated cadmium-induced memory impairment in rats. Results of the present study are discussed in term of cholinergic activity in cadmium-induced memory loss and its attenuation by nuts supplementation in rats

Development of AD like symptoms following co-administration of AlCl[3] and D-gal in rats: a neurochemical, biochemical and behavioural study

Alzheimer's disease [AD] is an age-related neurodegenerative disorder associated with neurochemical and neurobehavioural alterations. Aluminium [Al] is considered as a contributing factor in the etiology of several neurodegenerative disorders like AD. D-galactose [D-gal] is a physiological nutrient but over supply induces some neurochemical and biochemical changes that exacerbate natural aging process. In this study, we aimed to develop AD animal model by co-administration of Al and D-gal in rats. Male albino Wistar rats were intraperitoneally injected with AlCl[3] and D-gal at a dose of 150mg/kg and 300mg/kg respectively for one week. After one week rats were subjected to behavioural analysis. After behavioural analysis rats were decapitated to remove their brain. Biochemical and neurochemical analysis were conducted in whole brain. AlCl[3]+D-gal significantly induced depressive and anxious behaviour in rats. Rats cognitive abilities were also significantly impaired following AlCl[3] and D-gal co-administration. AlCl[3]+D-gal significantly altered antioxidant enzyme activities and biogenic amine levels in whole brain. A marked increase in brain lipid peroxidation and acetylcholinesterase activity was found in test rats. These findings suggest that co-administration of AlCl[3] and D-gal for one week could induce AD like symptoms and may be used to develop AD animal model

Impact of oral supplementation of Glutamate and GABA on memory performance and neurochemical profile in hippocampus of rats

Glutamate [GLU] and gamma-amino butyric acid [GABA] are essential amino acids [AA] for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water [control group] or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests [Novel object recognition test, Morris water maze, Passive avoidance test] measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine [ACh] were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance

Enhanced physical endurance and improved memory performance following taurine administration in rats

Energy drinks enhance physical endurance and cognitive ability. The ingredients present in these drinks are considered as ergogenic and have memory boosting effects. In the present study effects of taurine administration for one week was monitored on physical exercise and memory performance in rats. Animals were divided into two groups namely control and test. Taurine was injected intraperitoneally to the test group at the dose of 100mg/kg. After one week of treatment rats were subjected to physical exercise and memory task. Results of this study revealed that rats injected with taurine for one week exhibited improved muscular strength as well as enhanced memory performance in Morris water maze and elevated plus maze. Biomarker of lipid peroxidation was significantly reduced in brain and plasma of test animals. Taurine administration also resulted in higher levels of corticosterone in this study. The results highlight the significance of taurine ingestion in energy demanding and challenging situations in athletes and young subjects

Enriched environment palliates nicotine-induced addiction and associated neurobehavioral deficits in rats

This study was designed to investigate the role of enriched environment in preventing and/or reducing the neurobehavioral deficits produced after nicotine administration in albino Wistar rats. Equal numbers of rat in two groups were either placed in social environment [control group] or social along with physically enriched environment for four weeks before the administration of nicotine. Exposure to different environmental conditions was followed by the intraperitoneal injection of nicotine at the dose of 0.6 mg/kg for seven consecutive days during which addictive behavior was monitored using conditioned placed preference paradigm. Behavioral responses to locomotor activity, anxiety and retention of short term memory were investigated in control and nicotine injected groups exposed to different environments. Results of this study showed that the rats pre-exposed to physical along with social enrichment exhibited a decrease in drug seeking behavior, hyper locomotion, anxiogenic effects along with improvement of working memory as compared to control and nicotine injected groups that were kept in social environment alone. This behavioral study suggests that the exposure to physical enrichment along with socialization in young age can later reduce the chances of compulsive dependence on nicotine and related neurobehavioral deficits

Dizocilpine induced psychosis-like behavior in rats: a possible animal model with full spectrum of schizophrenia

Schizophrenia [SZ] is categorized as neuropsychiatric disorder with reduced lifespan and significant impairments in social and vocational functioning. One of the best proposed pharmacological animal models is dizocilpine, as it can mimic the full spectrum of schizophrenic disorder including positive and negative symptoms along with cognitive deficits. Dizocilpine is N-methyl-D-aspartate [NMDA] receptor antagonist known to induce hyperlocomotion and stereotyped behavior in rodents. Present study was designed to develop an animal model of SZ via intraperitoneal administration of dizocilpine in rats [100-150g] at a dose of 0.3 mg/kg for eight days. For the evaluation of positive symptoms, hyperlocomotor behavior was monitored. Negative symptoms were assessed by sucrose preference test [SPT] and social interaction test [SIT]. Moreover, Cognitive deficits were evaluated by novel object recognition test [NORT]. After behavioral assessments animals were decapitated for further evaluation of biochemical and neurochemical estimations. Present findings revealed that dizocilpine injected rats exhibited significant hyperlocomotor behavior, depressive symptoms and cognitive deficits. Results are further strengthened with a marked increase in lipid per oxidation [LPO] in brain and a decline in reduced glutathione [GSH] levels. Biogenic amine levels [Dopamine, DA; 5-hydroxytryptamine, 5-HT] were also significantly increased and decreased respectively. Thus, present findings suggest that dizocilpine can be used as one of the best drug to develop psychosis-like symptoms in rats and to develop an animal model following a short-term study

Enhancement in spatial and recognition memory functions following long term oral administration of ginger extract in rats

Ginger [Zingiber Officinale] is known over the centuries for its medicinal properties and has been used worldwide as health supplement and for treatment of several diseases. The purpose of this study was to evaluate the effects of whole ginger extract administration on spatial and recognition memory using experimental animal models. The antimicrobial properties of ginger extract against various pathogenic fungal and bacterial species were also examined. Aqueous extract of ginger at a dose of 500 mg/kg was orally administered to test rats and water was orally given to control rats for 6 weeks. Water Maze task [WM] was used to assess spatial memory and recognition memory of rats was evaluated by the Novel Object Recognition [NOR] task. Time spent with novel object was significantly increased in ginger treated rats as compared to control animals in novel object recognition task exhibiting enhanced recognition memory in ginger treated rats. Ginger treated rats exhibited significantly enhanced both short term memory and long term memory as evidenced by decrease in time to reach the hidden platform Ih and 24 h after training as compared to control rats. Short term memory functions of ginger treated rats were more enhanced than long term memory functions. Our findings suggest that ginger consumption may lead to an improvement in spatial and recognition memory. Significant activity of aqueous ginger extract was observed against pathogenic bacteria as well as fungal species. It is therefore suggested in this study that ginger extract can be used in microbial infections and as a memory enhancing drug in various memory disorders

Influence of serotonergic 5-HT2C receptor antagonist mesulergine in the reversal of memory deficits induced by mCPP

To determine the effect of non-selective 5-HT2C antagonist mesulergine and 5-HT2C agonist mCPP [metachlorophenylpiperazine] on learning acquisition [LA], short-term memory [STM] and long-term memory [LTM]. Experimental study. Department of Biochemistry, University of Karachi, from December 2009 to June 2010. Twenty-four male albino Wistar rats were used in this study. The agonist and antagonist [mCPP and mesulergine] were injected intraperitoneally at a dose 3.0 mg/kg in volumes of 1 ml/kg. Control animals were injected with saline [1 ml/kg]. Animals were randomly divided into four groups [n=6]. 1st being control group, 2nd being mCPP injected group, 3rd being mesulergine injected group and 4th group being injected with both mesulergine and mCPP. Behavioural activities of rats were monitored after 30 minutes of injection. For assessment of memory functions, water maze apparatus was used. Administration of mCPP impaired STM, LTM and LA of rats. Mesulergine injected rats exhibited no alteration in memory functions. However, when it was injected with mCPP then there were no memory deficits induced by mCPP. Ability of 5-HT2C receptor antagonist mesulergine to block the memory impairment effect of mCPP indicated an important regulatory role of 5-HT2C receptors in cognitive processes

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

m-Cpp induced hypolocomotion does not interfere in the assessment of memory functions in rats

Central serotonergic system plays a critical role in the regulation of memory processes in rats. Evidence suggests that a dysfunction of serotonergic system contributes to various pathological conditions. Among the multiple classes of serotonin [5-Hydroxytryptamine, 5-HT] receptors described in CNS, much attention has been devoted to the role of 5-HT2C receptor family on memory functions. A number of studies have shown that 5-HT2C receptor agonists impair memory function and also decreased locomotor activity of rats. The present study was designed to investigate the effect of different doses of 5-HT2C receptor agonist metachlorophenylpiperazine [mCPP] on locomotion and cognitive behavior in rats. Groups of adult male rats were injected mCPP intraperitoneally at doses of 1, 3 and 5 mg/kg. The learning and memory of rats were assessed by water maze [WM] and passive avoidance [PA] tests. Locomotor activity of rats was monitored by open field test. mCPP decreased locomotor activity of rats as reported earlier. A negative correlation between memory function and 5-HT2C receptor stimulation was observed in WM. Furthermore the administration of mCPP dose dependently impaired memory functions and the impairment of memory induced by mCPP was greatest at the highest dose. PA test was also performed in the present study to confirm that the decreased locomotor activity exhibited by mCPP injected rats did not affect the memory assessment in WM. Irrespective of hypolocomotion induced by mCPP, drug injected rats took less time to enter the punishable compartment which confirmed that the impairment in memory functions following mCPP was not due its effect on locomotion. It is suggested that 5-HT2C receptors might be involved in memory function probably mediating a suppressive or constraining action by decreasing dopamine levels. It can be therefore concluded that 5-HT2C receptors have a negative influence on memory function, which raises the possibility of using 5-HT2C receptor antagonists in the improvement of memory functions

Gender difference in memory functions following long term tryptophan supplementation in rats

Evidence shows that tryptophan [TRP] and serotonin [5HT] have a role in memory function. It has been shown in various studies that increase in serotonergic neurotransmissionis associated with increased memory consolidation whereas low brain 5HT impairs memory performance. In view of a possible role of TRP and 5HT in memory, the present study was designed to investigate the effect of TRP supplementation on male and female rats and to investigate sex related differences in memory processes. Tryptophan at a dose of 100mg/kg was used. Short term memory [STM] and long term memory [LTM] were evaluated using the Morris water maze. TRP treatment for 6 weeks significantly enhanced STM of female rats but it did not have any effect on the STM of male rats. Female rats when compared with male rats exhibited better performance in the Morris water maze and enhanced memory was observed both before and after TRP treatment, however after TRP treatment a greater improvement was observed. Both male and female rats exhibited improvement in LTM following TRP treatment. The present results emphasize on the involvement of sex difference and 5HT in learning and memory processes. A greater increase in 5HT metabolism and turnover seen in female rats correlates with the enhanced memory function observed in females than male rats

Relationship of brain tryptophan and serotonin in improving cognitive performance in rats

Brain function can be affected by the availability of dietary precursors of neurotransmitters. The diet induced increase in tryptophan [TRP] availability has been shown to increase brain serotonin synthesis and various related behaviors. Evidence shows that TRP and serotonin [5HT; 5 Hydroxytryptamine] play a significant role in memory function. Enhanced brain serotonin activity has been shown to improve cognitive performance in animals and human whereas decreasing brain 5HT levels by acute TRP depletion has been shown to impair cognition. A number of methods have been used for the assessment of memory in animals. In the present study, the radial arm maze and the passive avoidance was used for the assessment of memory in rats following long-term TRP administration. TRP at doses of 50 and 100 mg/kg body weight was orally administered for 6 weeks. The present study shows a significant improvement in memory of rats following both doses of tryptophan. Plasma TRP, brain TRP, 5HT and 5 hydroxy indol acetic acid [5HIAA] levels were increased significantly following administration of TRP. The results of the present study suggest that increase in brain 5HT metabolism following long term TRP administration may be involved in enhancement of memory