Memory enhancing and neuroprotective effects of apomorphine in a rat model of dementia.

Oxidative stress from generation of increased reactive oxygen species or has been reported to play an important role in dementia. Oxidative stress due to free radicals of oxygen or reactive oxygen species could be precipitating factors in the etiology of dementia. Apomorphine has been reported to have neuroprotective effects. To monitor memory enhancing and neuroprotective effects of apomorphine, we determined the antioxidant enzymes activities, lipid peroxidation, acetylcholine esterase (AChE) activity in brain and plasma, following repetitive administration of apomorphine in rat model of dementia. Biogenic amine levels were also monitored in hippocampus. Repeated administration of scopolamine was taken as an animal model of dementia. Decreased glutathione peroxidase, superoxide dismutase and catalase activities were observed in these animal models of dementia. While increased lipid peroxidation was also observed in the brain and plasma samples. The results showed significant effects of apomorphine. The activities of antioxidant enzymes displayed increased activities in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly higher in brain and plasma of apomorphine treated rats. Superoxide dismutase (SOD) was significantly decreased in plasma of scopolamine injected rats; and a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in scopolamine treated rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM). Short-term memory and long-term memory was impaired significantly in scopolamine treated rats, which was prevented by apomorphine. Moreover, a marked decrease in biogenic amines was also found in the brain of scopolamine treated rats and was reverted in apomorphine treated rats. Results showed that scopolamine-treatment induced memory impairment and induced oxidative stress in rats as compared to saline-treated controls. These impairments were significantly restored by apomorphine administration. In conclusion, our data suggests that apomorphine at the dose of 1 mg/kg could be a potential therapeutic agent to treat dementia and related disorders.

Co-treatment with low doses of buspirone prevents rewarding effects of methylphenidate and upregulates expression of 5-HT1A receptor mRNA in the nucleus accumbens.

Accumulating studies consistently show that methylphenidate (MPD), the first line drug for treating Attention-Deficit Hyperactivity Disorder (ADHD), is abused by patients to whom the drug is prescribed. Like other psychostimulants, only low doses of MPD improve cognitive performance while higher doses impair it. Preventing the use of high doses of MPD is important for retaining its therapeutic efficacy. Previously, it has been shown that performance in Morris water maze test is improved in rats treated, orally, with MPD in doses of 2.5 mg/kg; but higher doses (5 mg/kg) impair it. The present study is designed to monitor rewarding effects of 2.5 mg/kg MPD in conditioned place preference (CPP) paradigm and its potential inhibition in buspirone co-treated animals. Our results show that rewarding effects of MPD in CPP paradigm are prevented in rats co-treated with buspirone in doses of 0.1 and 0.3 mg/kg. Animals treated with MPD exhibit a downregulation of 5-HT1A receptor mRNA in the nucleus accumbens which is also prevented in rats co-treated with 0.1 and 0.3 mg/kg but not 1.0 and 2.0 mg/kg buspirone. Administration of buspirone in these doses is not rewarding in CPP test and upregulates 5-HT1A receptor mRNA in the nucleus accumbens. The findings suggest that co-use of low doses of buspirone can prevent rewarding effects of MPD to help retain its therapeutic efficacy.

Neurochemical and behavioral effects of fluoxetine on midazolam induce dependence in an animal model of addiction.

In the present study we have monitored effects of repeated coadministration of fluoxetine with midazolam; a benzodiazepine (CNS depressant). It is the primary drug of choice for procedural sedation, preoperative sedation, and in emergency departments. Repeated administration of this drug is reported to have abuse potential and may cause this by increasing dopaminergic neurotransmission. Since an important role of serotonin is there in the pathophysiology of anxiety and addiction, administration of midazolam may involve altered 5-HT metabolism as well. Present study was designed to monitor effects of repeated administration of fluoxetine with midazolam. Effects of fluoxetine and midazolam coadministration were monitored on motor activities in familiar and novel environments, hot plate test, forced swim test, conditioned place preference test and levels of dopamine, 5-HT and their metabolites. Both midazolam (2.5mg/kg) and fluoxetine (1mg/kg) were administered orally for 12 days. Conditioned place preference test was performed on day 13. Rats were decapitated and whole brain samples were collected and stored at -70°C until neurochemical analysis by HPLC-EC. Findings from the present study show attenuation of midazolam-induced reinforcement upon repeated co-administration of fluoxetine. These could be implicated to increased therapeutic utility of midazolam and related benzodiazepines.

Neurochemical and behavioral effects of lorazepam: A dose related study.

Present study was designed to monitor the dose dependent effects of lorazepam; a benzodiazepine (CNS depressant). It is the primary drug of choice for treatment of anxiety and to produce calming effects. However, repeated administration of this lorazepam causes dependence and this might be caused by increased dopaminergic neurotransmission. Besides dopamine, 5-hydroxy tryptamine (5-HT) has also been reported to have pivotal role in the pathophysiology as well as treatment of anxiety and addiction. Repeated administration of lorazepam might involve altered 5-HT metabolism as well. Present study was therefore designed to monitor dose-dependent effects of lorazepam and to select its optimum dose for further experiments and pharmacological interventions. Effects of lorazepam were monitored on food intake, growth rate, activities in familiar and novel environments, light dark box activity, forced swim test and metabolism of dopamine and 5-HT. oral administration of lorazepam was done at the doses of 0mg/kg, 2mg/kg, 4mg/kg and 6mg/kg. Behaviors parameters were monitored following single administration of lorazepam. Rats were decapitated and whole brain samples were collected and stored at -70°C until neurochemical analysis by HPLC-EC. Findings from the present study could be implicated to increased therapeutic utility of lorazepam and related benzodiazepines.

Dose related acute behavioral and neurochemical profile of pioglitazone.

Diabetics are twice as likely to have depression. It's normal to have long periods of sadness and anxiety. Pioglitazone has important role in the inflammatory response, which suggests that it might have the associated anti-depressant effects being manifested by its anti-depressant profile which needs further exploration. Monitoring changes in behavioral and neurochemical profile of pioglitazone in a dose-dependent manner was the purpose of this study. Pioglitazone was injected to rats at the doses of 0mg/kg, 2.5mg/kg, 5mg/kg and 10mg/kg. Behavioral activities in open field, Skinner's box and elevated plus maze were monitored 20, 35 and 45 minutes respectively after pioglitazone injection. whole brain samples were collected following decapitation of rats one-hour after injection. Samples were kept at -70ºC till HPLC-EC analysis for neurochemical profile. Results show anxiogenic and sedative effects of pioglitazone at all three doses as indicated by Skinner's box, elevated plus maze activity and open field. Also there was an overall decreased dopamine metabolism and increased serotonin turnover. This suggests that diabetic patients using pioglitazone as a therapeutic option, may experience more potent effects of CNS depressants. Findings may help in extending therapeutics in diabetic patients suffering from anxiety and/or depression.

Restraint-induced behavioral deficits are attenuated or impaired by pre- or post-injection of apomorphine: A context-based study.

Apomorphine, a psycho stimulant, has neuroprotective effects due to its ability to decrease oxidative stress. Stress-induced dopaminergic dysfunction might lead to posttraumatic stress disorder, depression and related disorders. This dopaminergic dysfunction is more pre-dominant in basal ganglia and prefrontal cortex. Targeting of this dysfunction by psychostimulants, involves elevating dopamine in these brain regions and reduction of stress. On the other hand, stress itself can aggravate addictive effects to psycho stimulants. Present study was therefore designed to monitor the role of apomorphine in the attenuation of stress-induced behavioral deficits. Rats were exposed to 2hr restraint stress either before or after the apomorphine administration, to monitor effects of apomorphine administration on stress-induced behavioral deficits. Stress-induced decreases in food intake, growth rate and elevated plus maze activity were exacerbated if apomorphine was experienced during restraint stress. Conversely, these behavioral deficits were attenuated if apomorphine was experienced after restraint stress. It shows that apomorphine, if experienced during restraint stress, produces greater behavioral deficits, while the same were attenuated in rats receiving apomorphine after the termination of restraint stress. Results suggest that apomorphine and possibly the other CNS stimulants may help to cope stress by attenuating stress-induced behavioral deficits, if experienced after stress.

Neurochemical and behavioral effects of midazolam: A dose related study.

In the present study we have monitored dose dependent effects of midazolam; a benzodiazepine (CNS depressant). It is the primary drug of choice for procedural sedation, preoperative sedation, and in emergency departments. Repeated administration of this drug is reported to have abuse potential and may cause this by increasing dopaminergic neurotransmission. Since an important role of 5-hydroxy tryptamine (5-HT) is there in the pathophysiology of anxiety and addiction, administration of midazolam may involve altered 5-HT metabolism as well. Present study was designed to monitor dose-dependent effects of midazolam and select the optimum dose for further experiments. Effects of midazolam were monitored on food intake, growth rate, activities in familiar and novel environments, light dark box activity, hot plate test, forced swim test and levels of dopamine, 5-HT and their metabolites. Midazolam was administered orally (0mg/kg, 2.5mg/kg, 5.0mg/kg and 10mg/kg) and behaviors were monitored post single midazolam administrations. Rats were decapitated and whole brain samples were collected and stored at -70°C until neurochemical analysis by HPLC-EC. Findings from the present study could be implicated to increased therapeutic utility of midazolam and related benzodiazepines.

Apomorphine-induced sensitization in rats exposed to restraint stress: Relationship with adaptation to stress.

Drug abuse and impaired adaptation to stress are inter-related. Drug abuse is more potentiated upon exposure to stress and an impairment to cope with stress may lead to depression. On the other hand, use of addictive compounds increase the vulnerability to depression by inhibiting the adaptation to stress. Present study investigates relationship between behavioral tolerance to repeated restraint stress and apomorphine-induced sensitization. Apomorphine was injected either before or after the restraint stress episode, to monitor drug-induced behavioral sensitization and place preference. Apomorphine-induced sensitization and place preference were enhanced if the drug is experiencing during restraint stress. Conversely, apomorphine-induced sensitization and place preference were attenuated if the drug is experiencing after restraint stress. It shows that apomorphine, if experienced during restraint stress, produces greater sensitization Conversely, sensitization effects of apomorphine are blocked in animals receiving apomorphine after the termination of restraint stress. The results tend to show that drug of abuse may be effective for the treatment but not prevention of stress-induced depression.

Enhancement and impairment of cognitive behaviour in Morris water maze test by methylphenidate to rats.

Methylphenidate (MPD), a psycho-stimulant is a prescription medicine for the treatment of Attention deficit hyperactivity disorder (ADHD). The drug is also being increasingly used by general population for enhancing cognition. Only few preclinical studies have been carried out on the effects of MPD on cognition and these studies show either an enhancement or impairment of memory following the administration of MPD. The present study was designed to evaluate the effects of different doses of methylphenidate on acquisition and retention of memory in Morris water-maze test. Twenty four male Albino Wistar rats (weighing 180-220gm) were randomly assigned to four groups: (1) Control (2) 0.5mg/kg (3) 2.5mg/kg (4) 5 mg/kg methylphenidate. Animals received drug or water orally before training phase. Memory acquisition was monitored 2hrs post drug administration while memory retention was determined next day. It was found that the clinically relevant doses of methylphenidate (0.5mg/kg and 2.5mg/kg) improved memory acquisition and its retention but higher dose (5mg/kg) impaired both. We suggest that MPD-induced increase of catecholamine neurotransmission may have a role in the improvement of water maze performance while agonist activity of the drug for 5HT-1A receptor in the impaired performance at high doses. Food intake and body weight changes were not affected by MPD administration due to short-term administration of the drug. Results may help in improving pharmaco-therapeutic use of MPD for ADHD.

Repeated treatment with a low dose of reserpine as a progressive model of Parkinson's dementia.

Present study was designed to monitor the cognitive profile of the animals upon repeated administration of reserpine, so as to determine that whether these animals should be used as animal models of Parkinson's dementia. In the present study, reserpine was injected daily (once a day for three weeks) at the dose of 0.1mg/kg. Short- and long term memories were assessed using a Morris water maze, on weekly basis. Novel object recognition test was performed after completion of the treatment (day 21). Animals were decapitated on day 21 and brain samples were stored at -70ºC until neurochemical analysis by HPLC-EC. Impairment of short- and long term activities (as monitored in Morris water maze) were not observed until after first week. Long term memory was found to be impaired earlier than the short term memory. Novel object recognition test also exhibited reserpine-induced impairment of working memory. Neurochemical analysis of the whole brain samples by HPLC-EC method showed that repeated administration of reserpine significantly increased DOPAC/ DA ratio (p<0.01). While 5-HIAA/ 5-HT ratio was found to be decreased (p<0.05) in reserpine injected animals. This further confirmed that these neurochemical deficits to be the underlying reason in memory impairment. In conclusion, present study provides evidence that repeated administration of reserpine can be used as a 'progressive' animal model of Parkinson's dementia. Results could be beneficial for face validity and screening of the drugs for the treatment of dementia secondary to Parkinson's and related disorders.

Effect of glycine: Studying memory and behavioral changes in mice.

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

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

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

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 -70οC 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.

Repeated treatment with reserpine as a progressive animal model of depression.

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

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.

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.

Behavioral, hormonal and central serotonin modulating effects of injected leptin.

Leptin is viewed as an important target for developing novel therapeutics for obesity, depression/anxiety and cognitive dysfunctions. The present study therefore concerns behavioral, hormonal and central serotonin modulating effects of systemically injected leptin. Pharmacological doses (100 and 500 µg/kg) of leptin injected systemically decreased 24h cumulative food intake and body weight in freely feeding rats and improved acquisition and retention of memory in Morris water maze test. Potential anxiety reducing, hormonal and serotonin modulating effects of the peptide hormone were determined in a separate experiment. Animals injected with 100 or 500 µg/kg leptin were tested for anxiety in an elevated plus maze test 1h later. A significant increase in the number of entries and time passed in open arm of the elevated plus maze in leptin injected animals suggested pronounced anxiety reducing effect. Moreover, circulating levels of leptin correlated significantly with anxiety reducing effects of the peptide hormone. Serum serotonin increased and ghrelin decreased in leptin injected animals and correlated, positively and negatively respectively, with circulating leptin. Corticosterone increased at low dose and levels were normal at higher dose. Serotonin metabolism in the hypothalamus and hippocampus decreased only at higher dose of leptin. The results support a role of leptin in the treatment of obesity, anxiety and cognitive dysfunctions. It is suggested that hormonal and serotonin modulating effects of leptin can alter treatment efficacy in particularly comorbid conditions.

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

Apomorphine, a dopamine D1/D2agonist, is an important drug of choice for the treatment of Parkinson's and related disorders. The present study was designed to perform the conformational analysis and geometry optimization of apomorphine. Resultant optimized structure corresponds to a substance as it is found in nature. This could be used for a variety of experimental and theoretical investigations especially in the field of pharmacokinetics. The results indicate that the best conformation of the molecule is present at minimum potential energy -88702.9595 kcal/mol. At this point molecule will be more active as histamine H1 receptor agonist.

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

A considerable body of literature suggests that depression and diabetes mellitus are co-morbid. The present study was designed to test any possible behavioral deficits and/or neurochemical changes in the brain as induced by the anti-diabetic drugs. Twenty-four rats were divided into four groups: (i) saline (ii) glimepiride (2.5mg/kg)- (iii) glimepiride (5.0mg/kg)- and (iv) glimepiride (10 mg/kg) injected animals. Behavioral activities in Skinner's box, open field and elevated plus maze were monitored 20, 35 and 45 minutes post injection respectively. Animals were decapitated 60 minutes post injection to collect brain samples. Samples were kept at -70°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 10mg/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 2.5 g/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 Ca²âº increased while that of K⁺ and Mg²âº decreased in the heart and kidney tissue. Ethanol administration also increased Na⁺ and Ca²âº levels and decreased K⁺ and Mg²âº levels in the heart and kidney tissue. Restraint stress decreased serum levels of Na⁺, K⁺, Ca²âº, P, and Cl⁻ and increased serum Mg²âº, glucose and haematocrit. Ethanol administration also decreased serum levels of Na⁺, K⁺, Ca²âº, P, and Cl⁻ and increased serum Mg²âº, 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.