... AND DECREASES OF OPEN FIELD LOCOMOTION FOLLOWING SINGLE AND REPEATED ADMINISTRATION OF HIGH D... more ... AND DECREASES OF OPEN FIELD LOCOMOTION FOLLOWING SINGLE AND REPEATED ADMINISTRATION OF HIGH DOSES OF CAFFEINE IN RATS Darakhshan J. Haleem, AnilaYasmeen, T. Parveen and ... CJ MELISKA, RE LANDRUM and TA LANDRUM, Pharmacol. ...
Tea consumption in many cases is the main source of caffeine intake in humans. In the present stu... more 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 ...
Objectives: To determine the factors associated with overweight and obesity among medical student... more Objectives: To determine the factors associated with overweight and obesity among medical students of public sector’s institutes in Karachi, Pakistan. Methodology: A university based cross-sectional analytic study was conducted in public sector institutes of Karachi. Data was collected from first year to final year medical students through convenient sampling technique by using self administered questionnaire followed by anthropometric measurement. The outcome variable “overweight or obesity” was defined by using South Asian BMI (≥ 23) cut-off points. Logistic regression technique was applied by using software SPSS to determine the factors associated with overweight and obesity among medical students. Results: A total of 428 medical students participated in study. Prevalence of overweight and obesity among medical students was found to be 14.7%, 12.4% respectively. Among boys it was 47.7% whereas among girls it was 15.9%. The prevalence of overweight and obesity was associated with ...
To assess the effectiveness of school-based interventions program in reducing the prevalence of o... more To assess the effectiveness of school-based interventions program in reducing the prevalence of overweight or obesity among schoolchildren. Ovid Medline (1950-December 2012), Embase (1980-2012), CINAHL (1982-2012), secondary references, review articles, and expert in the field. All published clinical trials were eligible for study if were randomized, methodologically strong-based on a validity assessment, aimed to evaluate a school-based intervention for childhood overweight or obesity, and measured outcome in term of prevalence/incidence difference in overweight and obesity among both groups. Studies involved in cost-effective analysis of school-based intervention have been excluded. Data from eligible studies abstracted and pooled for relative risk. Five trials with 3,904 schoolchildren were included. Mean age of the students (boys and girls) ranges 8.6-12.6 years. Meta-analysis showed a statistical significance beneficial effect of school-based intervention programs on obesity status of schoolchildren (risk ratio (RR) 0.58, 95% confidence interval (CI) 0.43-0.78) and suggested 42% reduction in prevalence of obesity among schoolchildren through school-based intervention programs. Individual studies also showed effectiveness of these school-based interventions. School-based intervention programs are effective in prevention of childhood overweight and obesity problem and our results quantitatively supported this argument.
Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by in... more 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...
To compare the long-term effects of carbamazepine (CBZ), valproic acid (VPA), and lamotrigine (LT... more To compare the long-term effects of carbamazepine (CBZ), valproic acid (VPA), and lamotrigine (LTG) as monotherapy on the markers of vascular risk. The present cross-sectional study was carried out at the Department of Neurology, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan, from 2012 to 2013. We selected 120 adult patients with epilepsy and 40 control subjects. The patients with epilepsy were divided into 3 groups according to the use of antiepileptic drugs (AEDs) (CBZ, n = 40; VPA, n = 40; and LTG, n = 40). All participants` total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL-c), high-density lipoprotein cholesterol (HDL-c), ratio of TC/HDL-c, ratio of LDL-c/HDL-c, body mass index (BMI), and blood pressure was determined. In patients with epilepsy, CBZ and VPA treatment caused a noteworthy increase in the concentrations of TG, TC, and LDL-c compared with LTG treatment and the control group (p<0.001). The HDL-c significantly decreased in CBZ, VPA, and LTG-treated patients as compared with controls (p<0.001). The ratio of LDL-c/HDL-c and TC/HDL-c significantly increased in VPA- and CBZ-treated groups compared with the LTG-treated, and control group, while the ratio was also considerably elevated in patients treated with CBZ as compared with the patients treated with VPA. The weight and BMI of the patients treated with AEDs were higher (p<0.01). Patients with epilepsy on CBZ or VPA have changed vascular risk markers that may lead to atherosclerosis, while LTG-treated patients have less alteration in lipid profile.
Cognitive decline is found to be a common feature of various neurological disorders like Alzheime... more Cognitive decline is found to be a common feature of various neurological disorders like Alzheimer's disease (AD). In order to recapitulate AD associated cognitive deficits and to plan therapeutic strategies researchers have developed various preclinical dementia models to recapitulate different aspects of cognitive domains affected in AD brain. So, the present study was aimed to compare alterations in previously reported dementia models i.e. pharmacological (Scopolamine-induced and corticosterone-induced), Environmental (Aluminium-induced and noise-stress) and physiological (natural aging) models in rats in a single experimental study across three cognitive domains spatial, recognition, and associative memory and associated alterations in their oxidative status and neurochemical profile to select appropriate dementia model. All groups received their respective treatments for 14days after which behavioural analysis was performed including Open Field test to assess ambulatory activity, Novel Object Recognition test, Morris Water Maze test and Passive Avoidance test for the assessment of recognition, spatial and associative memory. After monitoring the behavioural activities, rats were decapitated and their brains and hippocampus samples were collected for analysis of oxidative status and neurochemical profile. Results showed significant decline in different aspects of memory function in all dementia models which was more significant in scopolamine-injected rats. A significant decline in levels of monoamines and acetylcholine was also observed. In addition, significant alterations were also seen in oxidative profile indicating that cognitive decline could be associated with increased oxidative stress. Therefore, present findings highlight that for planning therapeutic strategies against cognitive dysfunctions, scopolamine-induced dementia model is the most appropriate dementia model to reveal AD-related cognitive impairment profile.
Repeated stress paradigms have been shown to cause devastating alterations on memory functions. S... more Repeated stress paradigms have been shown to cause devastating alterations on memory functions. Stress is linked with inflammation. Psychological and certain physical stressors could lead to neuroinflammation. Inflammatory process may occur by release of mediators and stimulate the production of prostaglandins through cyclooxygenase (COX). Treatment with COX inhibitors, which restrain prostaglandin production, has enhanced memory in a number of neuroinflammatory states showing a potential function for raised prostaglandins in these memory shortfalls. In the present study, potential therapeutic effects of indomethacin and diclofenac sodium on memory in both unrestraint and restraint rats were observed. Two components, long term memory and short term memory were examined by Morris water maze (MWM) and elevated plus maze (EPM) respectively. The present study also demonstrated the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on lipid peroxidation (LPO) and activities of antio...
The present study concerns responsiveness of pre-and postsynaptic 5-hydroxytryptamine (5-HT)-1A r... more The present study concerns responsiveness of pre-and postsynaptic 5-hydroxytryptamine (5-HT)-1A receptors in a rat model of tardive dyskinesia (TD). Vacuous chewing movements (VCMs) in rats are widely accepted as an animal model of TD. Results show that haloperidol injected at a dose of 1 mg/kg twice a day for 5 weeks elicited VCMs, which increased in a time dependent manner following the drug administration for 35 weeks. Tolerance was produced in motor coordination during the potentiation of VCMs. Exploratory activity in an open field and in an activity box decreased in haloperidol treated animals. The effects of 8-hydroxy-2-(di-npropylamino)tetraline (8-OH-DPAT; 0.5 mg/kg) were monitored 48-h after withdrawal from repeated administration of haloperidol. 8-OH-DPAT-induced locomotion was greater in haloperidol treated rats. 5-HT synthesis increased in haloperidol treated animals, while 8-OH-DPAT-induced decreases of 5-HT synthesis were greater in repeated haloperidol than repeated saline injected animals. The results suggest that an increase in the effectiveness of somatodendritic 5-HT-1A receptors may decrease the inhibitory influence of 5-HT on the activity of dopaminergic neurons to precipitate VCMs. The 5-HT-1A agonist may help to alleviate neuroleptic-induced TD.
Pakistan Journal of Pharmaceutical Sciences, Aug 1, 2004
Spiperone is a potent dopamine (DA) D 2 , serotonin (5-hydroxy tryptamine, 5-HT) 5-HT 1A and 5-HT... more Spiperone is a potent dopamine (DA) D 2 , serotonin (5-hydroxy tryptamine, 5-HT) 5-HT 1A and 5-HT 2A antagonist. It is used clinically as an antischizophrenic compound. Previous studies have shown that a downregulation of somatodendritic 5-HT 1A receptor is involved in adaptation to stress. The present study was designed to investigate the effects of spiperone administration on behavioral adaptation to an episode of restraint stress and on brain serotonin metabolism. Spiperone was administered to rats at a dose of 0.25 mg/kg/ml two times a day for two days. Saline or spiperone treated rats were restrained for 2h on day 2. Effects of restraint on food intake, water intake, growth rate, plus maze and open field activity were monitored on next day. All animals were killed after a restraint period of 2h on the 3rd day. An episode of 2h restraint decreased food intake, growth rate and water intake comparably in saline and spiperone treated rats. Open field activity was not altered by restraint stress or spiperone treatment. Plus maze activity decreased by restraint stress in saline but not spiperone treated rats. 5-HIAA levels increased in saline but not spiperone treated rats. The findings are discussed in the context of a role of serotonin and 5-HT 1A receptor antagonism in adaptation to stress.
Pakistan Journal of Pharmaceutical Sciences, Jul 1, 2014
Aging is a natural complex process that is regulated at genetic, cellular, molecular and systemic... more Aging is a natural complex process that is regulated at genetic, cellular, molecular and systemic levels and leads to the development of a variety of changes including structural, chemical and genetic in the senescent brain. The major goal of the present study was to investigate the age associated cognitive dysfunction and other behavioral changes and their association with age related alterations in levels of neurotransmitters, such as dopamine (DA) and serotonin (5-HT) in the hippocampal region. Twelve male Albino Wistar rats were taken for the study including six young rats (04-05 months old) and six aged (20-22 months old) rats in each group. The learning and memory performance of rats was assessed by passive avoidance test (PA) and novel objective recognition task (NOR). Ambulatory activity was monitored by Open field test. Light/Dark transition test was used to monitor anxiety, whereas depression like symptoms was examined by Forced Swim Test (FST). Results showed that aged rats exhibited learning and memory impairment in PA and NOR. There was a negative relation between aging process and locomotion, consistent with previous findings. Moreover, an augmented increase in level of anxiety and depression was also observed in senescent rats. A marked decrease in DA and 5-HT was observed in the hippocampus of aged rats. Similarly, levels of 5-HIAA and DOPAC were also found to be decreased in aged rats. It is therefore concluded that age has a negative influence on cognitive function, depression, anxiety and locomotion in rats. Cells in all brain regions, especially hippocampus are affected by aging. In general aging exhibits a decline in sensory, motor and cognitive functions. These behavioral changes or functional deficits may be attributed to the age related decline in the levels of different neurotransmitters in brain/hippocampus. The present findings of behavioral deficits and altered neurotransmission in hippocampus of aged rats suggest a relationship between senescence, altered brain neurotransmitters and behavioral deficits.
Caffeine administration has been shown to enhance performance and memory in rodents and humans wh... more 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.
Pakistan Journal of Pharmaceutical Sciences, Aug 1, 2006
Propranolol a β adrenergic antagonist, binds with 5-HT 1 receptor. 1-(1-naphthyl) piperazine (1-N... more Propranolol a β adrenergic antagonist, binds with 5-HT 1 receptor. 1-(1-naphthyl) piperazine (1-NP) a derivative of quipazine has serotonin antagonist activity at 5-HT 2 and agonist activity at 5-HT 1 site. In the present study neurochemical and behavioral effects of 1-NP was monitored in saline and propranolol injected rats. 1NP increased locomotor activity in saline as well as in propranolol injected rats. Administration of propranolol also increased locomotor activity and these increases were more enhanced following 1-NP administration. Levels of 5-HT were not altered following the administration of 1NP in saline as well as propranolol injected rats. 5-HT turnover however decreased by the administration of propranolol Adminstration of 1NP decreased 5-HT turnover in saline but not in propranolol injected rats.
Pakistan Journal of Pharmaceutical Sciences, Feb 1, 2003
Stress is a non-specific response of body to any physiological and psychological demand. Studies ... more Stress is a non-specific response of body to any physiological and psychological demand. Studies on experimental animals show that uncontrollable stress situation produce neurochemical and behavioral deficits In the present study effects of 2hrs. restraint stress were monitored on brain serotonin metabolism and memory in starved rats. An episode of 2hrs. restraint stress exhibited a significant decrease in food intake as well as in growth rate in starved rats. The memory function was significantly enhanced following 2hrs. restraint stress in starved rats. The concentration of Noradrenaline (NA) and Dihydroxyphenyl acetic acid (DOPAC) were increased in the brain while no effect of restraint stress was observed on brain Dopamine (DA) level. Brain levels of 5-hydroxy indoleacetic acid (5-HIAA) was significantly decreased in restraint rats. Tryptophan levels in brain as well as in plasma significantly decreased in starved rats following 2hrs. restraint stress. The findings are explained in terms of enhanced memory function following restrained stress which may be associated with a decrease in serotonergic function in starved rats.
Immobilization stress given for one hour decreased cumulative food intake and growth rate in rats... more Immobilization stress given for one hour decreased cumulative food intake and growth rate in rats. Activity in an open field scored next day was also smaller in the restrained animals. Stress is known to enhance brain serotonin (5-hydroxytryptamine; 5-HT) metabolism. It is however not clear, whether this enhancement is caused by an increase in the activity of tryptophan hydroxylase, the rate limiting enzyme of 5-HT biosynthesis or availability of the precursor tryptophan to the brain. In order to determine the utilization of tryptophan via serotonin path way in brain during stress; rats were injected with saline or tryptophan (50 mg/kg, i.p.). A group of both saline and tryptophan injected animals was restrained for one hour, while another group left unrestrained. The animals were killed immediately after the termination of stress period to collect plasma and brain samples. Injected tryptophan resulted in 3-4 fold rise of plasma tryptophan in both unstressed and stressed animals in one hour. Stress alone however had no effect on plasma total tryptophan concentration. Free tryptophan in plasma, brain tryptophan, 5-HT and 5-hydroxyindole acetic acid (5-HIAA) all increased by both stress and tryptophan injection. The increases of brain tryptophan, 5-HT and 5-HIAA but not of free tryptophan in plasma were considerably greater in restrained animals given tryptophan load. The results suggest that enhancement of brain serotonin metabolism during stress is caused by an increase in the availability of tryptophan to the brain as well as an increase in the activity of the enzyme tryptophan hydroxylase. Factors affecting the availability of tryptophan to the brain are discussed.
Numerous studies have consistently shown that repeated restraint stress produces functional neuro... more Numerous studies have consistently shown that repeated restraint stress produces functional neuromorphological and physiological alteration that are linked to the pathophysiology of brain disorder, like depression and bipolar disorder, causes alteration in cognition and learning memory. Lithium is the drug of choice in the treatment of depression and mania in bipolar disorder as a mood-stabilizing agent. Present study was designed to investigate the effects of long term lithium administration on memory function and its relation with 5-HT metabolism following repeated restraint stress. In this experiment memory was assessed by novel object recognition task in water treated and lithium treated unrestraint and restraint rats. Recognition memory decreased in water treated repeated restraint rats while in lithium treated repeated restraint rats recognition memory increased. 5-HIAA level increased in water treated restraint rats while decreased in lithium treated restraint rats. The findings indicate a role of brain serotonin in improved memory function in repeated restraint rats following long term lithium administration.
The effects of buspirone (0.5 mg/kg) on the neuroendocrine and serotonergic responses to stress w... more The effects of buspirone (0.5 mg/kg) on the neuroendocrine and serotonergic responses to stress were monitored in rats. Exposure to 2-h of restraint stress increased circulating levels of corticosterone, noradrenaline and glucose. The metabolism of 5-hydroxytryptamine (5-HT; serotonin) increased in the brain. Prior administration of buspirone did not alter levels of corticosterone, noradrenaline and glucose in unrestrained rats, but inhibited stress-induced increase in the activity of hypothalamic-pituitary-adrenal (HPA) axis and circulating levels of glucose. Restraint-induced rise in brain 5-HT and 5-hydroxyindole-acetic acid (5-HIAA) was also attenuated by buspirone. Unrestrained animals injected with buspirone also exhibited a decrease in brain 5-HIAA concentration. The findings are discussed in the context of the role of somatodendritic 5-HT ) receptors in responses to stress.
Pakistan Journal of Pharmaceutical Sciences, Apr 1, 2009
The black cumin or Nigella sativa L. seeds have many acclaimed medicinal properties. Pharmacologi... more 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.
... AND DECREASES OF OPEN FIELD LOCOMOTION FOLLOWING SINGLE AND REPEATED ADMINISTRATION OF HIGH D... more ... AND DECREASES OF OPEN FIELD LOCOMOTION FOLLOWING SINGLE AND REPEATED ADMINISTRATION OF HIGH DOSES OF CAFFEINE IN RATS Darakhshan J. Haleem, AnilaYasmeen, T. Parveen and ... CJ MELISKA, RE LANDRUM and TA LANDRUM, Pharmacol. ...
Tea consumption in many cases is the main source of caffeine intake in humans. In the present stu... more 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 ...
Objectives: To determine the factors associated with overweight and obesity among medical student... more Objectives: To determine the factors associated with overweight and obesity among medical students of public sector’s institutes in Karachi, Pakistan. Methodology: A university based cross-sectional analytic study was conducted in public sector institutes of Karachi. Data was collected from first year to final year medical students through convenient sampling technique by using self administered questionnaire followed by anthropometric measurement. The outcome variable “overweight or obesity” was defined by using South Asian BMI (≥ 23) cut-off points. Logistic regression technique was applied by using software SPSS to determine the factors associated with overweight and obesity among medical students. Results: A total of 428 medical students participated in study. Prevalence of overweight and obesity among medical students was found to be 14.7%, 12.4% respectively. Among boys it was 47.7% whereas among girls it was 15.9%. The prevalence of overweight and obesity was associated with ...
To assess the effectiveness of school-based interventions program in reducing the prevalence of o... more To assess the effectiveness of school-based interventions program in reducing the prevalence of overweight or obesity among schoolchildren. Ovid Medline (1950-December 2012), Embase (1980-2012), CINAHL (1982-2012), secondary references, review articles, and expert in the field. All published clinical trials were eligible for study if were randomized, methodologically strong-based on a validity assessment, aimed to evaluate a school-based intervention for childhood overweight or obesity, and measured outcome in term of prevalence/incidence difference in overweight and obesity among both groups. Studies involved in cost-effective analysis of school-based intervention have been excluded. Data from eligible studies abstracted and pooled for relative risk. Five trials with 3,904 schoolchildren were included. Mean age of the students (boys and girls) ranges 8.6-12.6 years. Meta-analysis showed a statistical significance beneficial effect of school-based intervention programs on obesity status of schoolchildren (risk ratio (RR) 0.58, 95% confidence interval (CI) 0.43-0.78) and suggested 42% reduction in prevalence of obesity among schoolchildren through school-based intervention programs. Individual studies also showed effectiveness of these school-based interventions. School-based intervention programs are effective in prevention of childhood overweight and obesity problem and our results quantitatively supported this argument.
Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by in... more 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...
To compare the long-term effects of carbamazepine (CBZ), valproic acid (VPA), and lamotrigine (LT... more To compare the long-term effects of carbamazepine (CBZ), valproic acid (VPA), and lamotrigine (LTG) as monotherapy on the markers of vascular risk. The present cross-sectional study was carried out at the Department of Neurology, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan, from 2012 to 2013. We selected 120 adult patients with epilepsy and 40 control subjects. The patients with epilepsy were divided into 3 groups according to the use of antiepileptic drugs (AEDs) (CBZ, n = 40; VPA, n = 40; and LTG, n = 40). All participants` total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL-c), high-density lipoprotein cholesterol (HDL-c), ratio of TC/HDL-c, ratio of LDL-c/HDL-c, body mass index (BMI), and blood pressure was determined. In patients with epilepsy, CBZ and VPA treatment caused a noteworthy increase in the concentrations of TG, TC, and LDL-c compared with LTG treatment and the control group (p&amp;amp;amp;amp;lt;0.001). The HDL-c significantly decreased in CBZ, VPA, and LTG-treated patients as compared with controls (p&amp;amp;amp;amp;lt;0.001). The ratio of LDL-c/HDL-c and TC/HDL-c significantly increased in VPA- and CBZ-treated groups compared with the LTG-treated, and control group, while the ratio was also considerably elevated in patients treated with CBZ as compared with the patients treated with VPA. The weight and BMI of the patients treated with AEDs were higher (p&amp;amp;amp;amp;lt;0.01). Patients with epilepsy on CBZ or VPA have changed vascular risk markers that may lead to atherosclerosis, while LTG-treated patients have less alteration in lipid profile.
Cognitive decline is found to be a common feature of various neurological disorders like Alzheime... more Cognitive decline is found to be a common feature of various neurological disorders like Alzheimer&amp;amp;amp;amp;amp;amp;#39;s disease (AD). In order to recapitulate AD associated cognitive deficits and to plan therapeutic strategies researchers have developed various preclinical dementia models to recapitulate different aspects of cognitive domains affected in AD brain. So, the present study was aimed to compare alterations in previously reported dementia models i.e. pharmacological (Scopolamine-induced and corticosterone-induced), Environmental (Aluminium-induced and noise-stress) and physiological (natural aging) models in rats in a single experimental study across three cognitive domains spatial, recognition, and associative memory and associated alterations in their oxidative status and neurochemical profile to select appropriate dementia model. All groups received their respective treatments for 14days after which behavioural analysis was performed including Open Field test to assess ambulatory activity, Novel Object Recognition test, Morris Water Maze test and Passive Avoidance test for the assessment of recognition, spatial and associative memory. After monitoring the behavioural activities, rats were decapitated and their brains and hippocampus samples were collected for analysis of oxidative status and neurochemical profile. Results showed significant decline in different aspects of memory function in all dementia models which was more significant in scopolamine-injected rats. A significant decline in levels of monoamines and acetylcholine was also observed. In addition, significant alterations were also seen in oxidative profile indicating that cognitive decline could be associated with increased oxidative stress. Therefore, present findings highlight that for planning therapeutic strategies against cognitive dysfunctions, scopolamine-induced dementia model is the most appropriate dementia model to reveal AD-related cognitive impairment profile.
Repeated stress paradigms have been shown to cause devastating alterations on memory functions. S... more Repeated stress paradigms have been shown to cause devastating alterations on memory functions. Stress is linked with inflammation. Psychological and certain physical stressors could lead to neuroinflammation. Inflammatory process may occur by release of mediators and stimulate the production of prostaglandins through cyclooxygenase (COX). Treatment with COX inhibitors, which restrain prostaglandin production, has enhanced memory in a number of neuroinflammatory states showing a potential function for raised prostaglandins in these memory shortfalls. In the present study, potential therapeutic effects of indomethacin and diclofenac sodium on memory in both unrestraint and restraint rats were observed. Two components, long term memory and short term memory were examined by Morris water maze (MWM) and elevated plus maze (EPM) respectively. The present study also demonstrated the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on lipid peroxidation (LPO) and activities of antio...
The present study concerns responsiveness of pre-and postsynaptic 5-hydroxytryptamine (5-HT)-1A r... more The present study concerns responsiveness of pre-and postsynaptic 5-hydroxytryptamine (5-HT)-1A receptors in a rat model of tardive dyskinesia (TD). Vacuous chewing movements (VCMs) in rats are widely accepted as an animal model of TD. Results show that haloperidol injected at a dose of 1 mg/kg twice a day for 5 weeks elicited VCMs, which increased in a time dependent manner following the drug administration for 35 weeks. Tolerance was produced in motor coordination during the potentiation of VCMs. Exploratory activity in an open field and in an activity box decreased in haloperidol treated animals. The effects of 8-hydroxy-2-(di-npropylamino)tetraline (8-OH-DPAT; 0.5 mg/kg) were monitored 48-h after withdrawal from repeated administration of haloperidol. 8-OH-DPAT-induced locomotion was greater in haloperidol treated rats. 5-HT synthesis increased in haloperidol treated animals, while 8-OH-DPAT-induced decreases of 5-HT synthesis were greater in repeated haloperidol than repeated saline injected animals. The results suggest that an increase in the effectiveness of somatodendritic 5-HT-1A receptors may decrease the inhibitory influence of 5-HT on the activity of dopaminergic neurons to precipitate VCMs. The 5-HT-1A agonist may help to alleviate neuroleptic-induced TD.
Pakistan Journal of Pharmaceutical Sciences, Aug 1, 2004
Spiperone is a potent dopamine (DA) D 2 , serotonin (5-hydroxy tryptamine, 5-HT) 5-HT 1A and 5-HT... more Spiperone is a potent dopamine (DA) D 2 , serotonin (5-hydroxy tryptamine, 5-HT) 5-HT 1A and 5-HT 2A antagonist. It is used clinically as an antischizophrenic compound. Previous studies have shown that a downregulation of somatodendritic 5-HT 1A receptor is involved in adaptation to stress. The present study was designed to investigate the effects of spiperone administration on behavioral adaptation to an episode of restraint stress and on brain serotonin metabolism. Spiperone was administered to rats at a dose of 0.25 mg/kg/ml two times a day for two days. Saline or spiperone treated rats were restrained for 2h on day 2. Effects of restraint on food intake, water intake, growth rate, plus maze and open field activity were monitored on next day. All animals were killed after a restraint period of 2h on the 3rd day. An episode of 2h restraint decreased food intake, growth rate and water intake comparably in saline and spiperone treated rats. Open field activity was not altered by restraint stress or spiperone treatment. Plus maze activity decreased by restraint stress in saline but not spiperone treated rats. 5-HIAA levels increased in saline but not spiperone treated rats. The findings are discussed in the context of a role of serotonin and 5-HT 1A receptor antagonism in adaptation to stress.
Pakistan Journal of Pharmaceutical Sciences, Jul 1, 2014
Aging is a natural complex process that is regulated at genetic, cellular, molecular and systemic... more Aging is a natural complex process that is regulated at genetic, cellular, molecular and systemic levels and leads to the development of a variety of changes including structural, chemical and genetic in the senescent brain. The major goal of the present study was to investigate the age associated cognitive dysfunction and other behavioral changes and their association with age related alterations in levels of neurotransmitters, such as dopamine (DA) and serotonin (5-HT) in the hippocampal region. Twelve male Albino Wistar rats were taken for the study including six young rats (04-05 months old) and six aged (20-22 months old) rats in each group. The learning and memory performance of rats was assessed by passive avoidance test (PA) and novel objective recognition task (NOR). Ambulatory activity was monitored by Open field test. Light/Dark transition test was used to monitor anxiety, whereas depression like symptoms was examined by Forced Swim Test (FST). Results showed that aged rats exhibited learning and memory impairment in PA and NOR. There was a negative relation between aging process and locomotion, consistent with previous findings. Moreover, an augmented increase in level of anxiety and depression was also observed in senescent rats. A marked decrease in DA and 5-HT was observed in the hippocampus of aged rats. Similarly, levels of 5-HIAA and DOPAC were also found to be decreased in aged rats. It is therefore concluded that age has a negative influence on cognitive function, depression, anxiety and locomotion in rats. Cells in all brain regions, especially hippocampus are affected by aging. In general aging exhibits a decline in sensory, motor and cognitive functions. These behavioral changes or functional deficits may be attributed to the age related decline in the levels of different neurotransmitters in brain/hippocampus. The present findings of behavioral deficits and altered neurotransmission in hippocampus of aged rats suggest a relationship between senescence, altered brain neurotransmitters and behavioral deficits.
Caffeine administration has been shown to enhance performance and memory in rodents and humans wh... more 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.
Pakistan Journal of Pharmaceutical Sciences, Aug 1, 2006
Propranolol a β adrenergic antagonist, binds with 5-HT 1 receptor. 1-(1-naphthyl) piperazine (1-N... more Propranolol a β adrenergic antagonist, binds with 5-HT 1 receptor. 1-(1-naphthyl) piperazine (1-NP) a derivative of quipazine has serotonin antagonist activity at 5-HT 2 and agonist activity at 5-HT 1 site. In the present study neurochemical and behavioral effects of 1-NP was monitored in saline and propranolol injected rats. 1NP increased locomotor activity in saline as well as in propranolol injected rats. Administration of propranolol also increased locomotor activity and these increases were more enhanced following 1-NP administration. Levels of 5-HT were not altered following the administration of 1NP in saline as well as propranolol injected rats. 5-HT turnover however decreased by the administration of propranolol Adminstration of 1NP decreased 5-HT turnover in saline but not in propranolol injected rats.
Pakistan Journal of Pharmaceutical Sciences, Feb 1, 2003
Stress is a non-specific response of body to any physiological and psychological demand. Studies ... more Stress is a non-specific response of body to any physiological and psychological demand. Studies on experimental animals show that uncontrollable stress situation produce neurochemical and behavioral deficits In the present study effects of 2hrs. restraint stress were monitored on brain serotonin metabolism and memory in starved rats. An episode of 2hrs. restraint stress exhibited a significant decrease in food intake as well as in growth rate in starved rats. The memory function was significantly enhanced following 2hrs. restraint stress in starved rats. The concentration of Noradrenaline (NA) and Dihydroxyphenyl acetic acid (DOPAC) were increased in the brain while no effect of restraint stress was observed on brain Dopamine (DA) level. Brain levels of 5-hydroxy indoleacetic acid (5-HIAA) was significantly decreased in restraint rats. Tryptophan levels in brain as well as in plasma significantly decreased in starved rats following 2hrs. restraint stress. The findings are explained in terms of enhanced memory function following restrained stress which may be associated with a decrease in serotonergic function in starved rats.
Immobilization stress given for one hour decreased cumulative food intake and growth rate in rats... more Immobilization stress given for one hour decreased cumulative food intake and growth rate in rats. Activity in an open field scored next day was also smaller in the restrained animals. Stress is known to enhance brain serotonin (5-hydroxytryptamine; 5-HT) metabolism. It is however not clear, whether this enhancement is caused by an increase in the activity of tryptophan hydroxylase, the rate limiting enzyme of 5-HT biosynthesis or availability of the precursor tryptophan to the brain. In order to determine the utilization of tryptophan via serotonin path way in brain during stress; rats were injected with saline or tryptophan (50 mg/kg, i.p.). A group of both saline and tryptophan injected animals was restrained for one hour, while another group left unrestrained. The animals were killed immediately after the termination of stress period to collect plasma and brain samples. Injected tryptophan resulted in 3-4 fold rise of plasma tryptophan in both unstressed and stressed animals in one hour. Stress alone however had no effect on plasma total tryptophan concentration. Free tryptophan in plasma, brain tryptophan, 5-HT and 5-hydroxyindole acetic acid (5-HIAA) all increased by both stress and tryptophan injection. The increases of brain tryptophan, 5-HT and 5-HIAA but not of free tryptophan in plasma were considerably greater in restrained animals given tryptophan load. The results suggest that enhancement of brain serotonin metabolism during stress is caused by an increase in the availability of tryptophan to the brain as well as an increase in the activity of the enzyme tryptophan hydroxylase. Factors affecting the availability of tryptophan to the brain are discussed.
Numerous studies have consistently shown that repeated restraint stress produces functional neuro... more Numerous studies have consistently shown that repeated restraint stress produces functional neuromorphological and physiological alteration that are linked to the pathophysiology of brain disorder, like depression and bipolar disorder, causes alteration in cognition and learning memory. Lithium is the drug of choice in the treatment of depression and mania in bipolar disorder as a mood-stabilizing agent. Present study was designed to investigate the effects of long term lithium administration on memory function and its relation with 5-HT metabolism following repeated restraint stress. In this experiment memory was assessed by novel object recognition task in water treated and lithium treated unrestraint and restraint rats. Recognition memory decreased in water treated repeated restraint rats while in lithium treated repeated restraint rats recognition memory increased. 5-HIAA level increased in water treated restraint rats while decreased in lithium treated restraint rats. The findings indicate a role of brain serotonin in improved memory function in repeated restraint rats following long term lithium administration.
The effects of buspirone (0.5 mg/kg) on the neuroendocrine and serotonergic responses to stress w... more The effects of buspirone (0.5 mg/kg) on the neuroendocrine and serotonergic responses to stress were monitored in rats. Exposure to 2-h of restraint stress increased circulating levels of corticosterone, noradrenaline and glucose. The metabolism of 5-hydroxytryptamine (5-HT; serotonin) increased in the brain. Prior administration of buspirone did not alter levels of corticosterone, noradrenaline and glucose in unrestrained rats, but inhibited stress-induced increase in the activity of hypothalamic-pituitary-adrenal (HPA) axis and circulating levels of glucose. Restraint-induced rise in brain 5-HT and 5-hydroxyindole-acetic acid (5-HIAA) was also attenuated by buspirone. Unrestrained animals injected with buspirone also exhibited a decrease in brain 5-HIAA concentration. The findings are discussed in the context of the role of somatodendritic 5-HT ) receptors in responses to stress.
Pakistan Journal of Pharmaceutical Sciences, Apr 1, 2009
The black cumin or Nigella sativa L. seeds have many acclaimed medicinal properties. Pharmacologi... more 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.
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