ABSTRACT
OBJECTIVES: The purpose of the present study was to investigate the association between -1438A/G polymorphism of 5-HT2A receptor gene and schizophrenia in Korean and Han Chinese population. METHODS: A sample of 184 Korean patients with schizophrenia and 96 Korean healthy normal controls and 96 Han Chinese patients with schizophrenia and 96 Han-Chinese healthy normal controls were genotyped for a single nucleotide polymorphism with in 5-HT2A receptor gene (promoter region, A-1438G) by Msp I Restriction Fragment Length Polymorphism (RFLP). RESULTS: There was no difference in allelic frequencies and genotype frequencies of -1438A/G polymorphism between Korean schizophrenics and controls (p=0.13) and Han Chinese schizophrenics and controls (p=0.40). Also, -1438A/G polymorphism did not show ethnical difference between Korean and Han Chinese controls. The Scale for the Assessment of Negative Symptoms (SANS) scores showed no significant differences between genotypes of -1438A/G polymorphism in both of Korean and Han Chinese schizophrenics. CONCLUSION: These results suggest that -1438A/G polymorphism of the 5-HT2A receptor gene is not causally related to the development of schizophrenia in Korean and Han Chinese population, and there no ethnic difference between Korean and Han Chinese population.
Subject(s)
Humans , Asian People , Genotype , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Receptor, Serotonin, 5-HT2A , SchizophreniaABSTRACT
OBJECTIVES: The purpose of the present study was to investigate the association between -1438A/G polymorphism of 5-HT2A receptor gene and schizophrenia in Korean and Han Chinese population. METHODS: A sample of 184 Korean patients with schizophrenia and 96 Korean healthy normal controls and 96 Han Chinese patients with schizophrenia and 96 Han-Chinese healthy normal controls were genotyped for a single nucleotide polymorphism with in 5-HT2A receptor gene (promoter region, A-1438G) by Msp I Restriction Fragment Length Polymorphism (RFLP). RESULTS: There was no difference in allelic frequencies and genotype frequencies of -1438A/G polymorphism between Korean schizophrenics and controls (p=0.13) and Han Chinese schizophrenics and controls (p=0.40). Also, -1438A/G polymorphism did not show ethnical difference between Korean and Han Chinese controls. The Scale for the Assessment of Negative Symptoms (SANS) scores showed no significant differences between genotypes of -1438A/G polymorphism in both of Korean and Han Chinese schizophrenics. CONCLUSION: These results suggest that -1438A/G polymorphism of the 5-HT2A receptor gene is not causally related to the development of schizophrenia in Korean and Han Chinese population, and there no ethnic difference between Korean and Han Chinese population.
Subject(s)
Humans , Asian People , Genotype , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Receptor, Serotonin, 5-HT2A , SchizophreniaABSTRACT
OBJECTIVE: The association of neurotrophic factors with the etiology of schizophrenia has been widely studied. Among them, glial cell line-derived neurotrophic factor (GDNF) is known to promote the survival and differentiation of dopaminergic neurons. Considering dopamine hypothesis and neurodevelopmental theory, GDNF gene may be related with schizophrenia. In this study, we tried to clarify the association between schizophrenia and GDNF gene polymorphism. METHODS: Genotype and allele frequencies in the promoter and intron regions of GDNF gene were studied by using restriction fragment length polymorphism to compare 180 Korean schizophrenics with 105 Korean controls. RESULTS: We found significant differences between the schizophrenics and the controls in genotype and allele frequencies of BsaI polymorphism in the promoter region of GDNF gene (x2=18.208, df=2, p=0.0001/x2=11.264, df=1, p=0.0008). But no significant differences were found in intron region (p=0.06, p=0.984). CONCLUSION: These results suggest that polymorphism of GDNF gene might be related to the pathogenesis of schizophrenia.
Subject(s)
Dopamine , Dopaminergic Neurons , Gene Frequency , Genotype , Glial Cell Line-Derived Neurotrophic Factor , Introns , Nerve Growth Factors , Polymorphism, Restriction Fragment Length , Promoter Regions, Genetic , SchizophreniaABSTRACT
This study was designed to evaluated the effects of opioid receptor agonists on the spontaneous alternation behaviour in an animal model of obsessive-compulsive disorder in rats. According to the theory that dopamine is related to the biological etiology of obsessive-compulsive disorder, the effect of the nalbuphine(opioid kappa agonist) and the tramadol(opioid mu agonist), which act as manipulating agents on the inhibition or stimulation of dopamine release, in the spontaneous alternation behaviour were evaluated. 24 hours prior to the experiment, rats were food-deprived. These rats were put into the T-maze, in which white and black goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for each time. After identifying the stable baseline of spontaneous alternation behaviour, nonselective 5-HT agonist 5-MeODMT(1.25mg/kg/IP) disrupted spontaneous alternation. Rats were stratified into fluoxetine(10mg/kg/IP), nalbuphine(10mg/kg/IP), tramadol(46.4mg/kg/IP), and saline(0.5cc/IP) injection group with experimental drug treatment for 21 days. The effects on the 5-M?DMT(1.25mg/kg/IP) induced disruption of spontaneous alternation behaviour were checked at the next day of discontinuation of drug treatment. The results were as follows : 1) At the day after 21 days of the drug treatment, the nalbuphine treated group and the fluoxetine treated group showed significant difference from the tramadol treated group and the saline treated group in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. 2) Within each drug treatment group, the fluoxetine treated group showed significant difference between before and after the treatment of fluoxetine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. And also, the nalbuphine treated group showed significant difference between before and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. There was no difference between the baseline and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. We indentified that the opioid kappa agonist that act as dopamine release inhibitor affect the spontaneous alternation behaviour which is an animal model of obsessive-compulsive disorder in rat.
Subject(s)
Animals , Rats , Cacao , Dopamine , Fluoxetine , Milk , Models, Animal , Nalbuphine , Obsessive-Compulsive Disorder , Receptors, Opioid , Serotonin Receptor Agonists , TramadolABSTRACT
OBJECT: This study was designed to evaluate the effects of olanzapine on the schedule-induced polydipsia(SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered olanzapine as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol for the dopamine antagonist to rats which showed schedule-induced polydipsic behavior. METHODS: Spraque-Dawley rats weighing 200-250gm were individually housed and maintained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds(FT-60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior(greater than 3 times of water per session on average). 5 groups of rats were administered olanzapine(3mg/kg, i.p), olanzapine(10mg/kg, i.p), fluoxetine(5mg/kg, i.p.), haloperidol(0.1mg/kg, i.o), and vehicle(1cc/kg, i.p) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighted before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a post-hoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats(N=8) were individually housed and given a single bolus(14.5gm) of food per day which maintained them at their average body weight. RESULTS AND CONCLUSION: There results were as follows : 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake over the 3 weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 3mg group showed significant decrease in the amount of water intake at 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 10mg group showed significant decrease in the amount of water intake at 2nd and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their average amount of polydipsic water intakes. 3) The fluoxetine group showed significantly lower amounts of water intake than the haloperidol group at 2nd weeks of drug treatment. And also the fluoxetine group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. The olanzapine 3mg group and the olanzapine 10mg group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. Above findings suggest that the fixed time feeding procedure for schedule-induced polydipsia as an animal model of obsessive compulsive disorder was effective to the evaluation of pharmacological challenge study. The authors assume that the serotonin hypothesis and the serotonin-dopamine interaction hypothesis are preferred to the dopamine hypothesis in the biological etiology of obsessive-compulsive disorder.
Subject(s)
Animals , Rats , Appointments and Schedules , Body Weight , Diet , Dopamine , Drinking , Fluoxetine , Haloperidol , Models, Animal , Obsessive-Compulsive Disorder , Polydipsia , Serotonin , WaterABSTRACT
OBJECTIVES: Phencyclidine(PCP) or PCP-like substances such as ketamine have been know to rekindle the cognitive dysfunction in schizophrenia. The aims of this study were to identify whether PCP-like substances can produce cognitive deficit in schizophrenia, to discuss relation with aging process, and finally to speculate underlying neurochemical mecha-nisms by various drug responses. METHODS: In experiment I, radial maze tests were done in 24 Sprague-Dawley rats for 3 days to get baseline data. Being divided into 4 groups(6 rats respectively) of normal aged, normal adult controls, atropine-treated and ketamine-treated, the radial maze tests were repeated on every week for 6 weeks, and then the rats were sacrificed by intracardiac perfusion with phosphate-buffered 10% formaldehyde solution for histology. The brain specimen was stained with hematoxylin-eosin to count cells in the prefrontal cortex and hippocampus. In experiment II, radial maze tests were done for 48 rats before any drug treatment and only after ketamine administration. Thereafter, haloperidol, bromocriptine, clonidine, nimodipine, tacrine, valproic acid, naloxone and fluoxetine were intramuscularly injected on every other day in addition to ketamine. Radial maze tests were repeated on every week for 6 weeks, and then rats were prepared by the same procedure for histology. RESULTS: 1) Reaction times of radial maze tests of atropine-treated rats were significantly prolonged than those of normal aged(p<0.05) or normal adult controls(p<0.05). Cell numbers of prefrontal cortex & hippocampus in ketamine-treated rats were significantly reduced than those in normal aged(p<0.05) or normal adult controls(p<0.005). 2) Reduced cell numbers by ketamine became significantly raised by tacrine administration in prefrontal cortex $ hippocampus(p<0.05), while there were no significant changes on radial maze test. Cell numbers also tended to be raised by nimodipine, fluoxetine and haloperidol administration. CONCLUSIONS: In conclusion, the visuospatial memory disorders in ketamine-induced psychotic rats might be partly associated with aging process. Furthermore, the responses to the various drugs suggested cholinergic system might have an important role in the neurochemical mechanism of the cognitive dysfunction in ketamine-induced psychosis. Otherwise, calcium metabolism as well as serotonergic and dopaminergic systems seemed to be possibly related.
Subject(s)
Adult , Animals , Humans , Rats , Acetylcholine , Aging , Brain , Bromocriptine , Calcium , Cell Count , Clonidine , Fluoxetine , Formaldehyde , Haloperidol , Hippocampus , Ketamine , Memory Disorders , Metabolism , Models, Animal , Naloxone , Nimodipine , Perfusion , Prefrontal Cortex , Psychotic Disorders , Rats, Sprague-Dawley , Reaction Time , Schizophrenia , Tacrine , Valproic AcidABSTRACT
About 40% of patients suffering from postencephalitic or idiopathic parkinsonism experience distressing and ill-defined sensations. Antipsychotic-induced acute extrapyramidal syndromes (EFSs) share phenomenological, pharmacological, and biochemical characteristics with these parkinsonisms. Thus, it is conceivable that antipsychotic-induced acute EPSs may also be associated with primary sensory symptoms. The aim of this study was to test this hypothesis, first by examining the frequency and risk factors of primary sensory symptoms and then by contrasting the clinical characteristics in patients with or without antipsychotic-induced acute EFSs and in patients who did or did not report sensory symptoms. The study group comprised 107 patients who receiving antipsychotics. The authors used DSM-IV criteria and Yale Extrapyamidal Symptom Scale for acute EFSs and modified McGill Pain Questionnaire for sensory symptoms. The results were as follows: 1) Twenty-one(19.6%) of 107 patients receiving antipsychotics reported sensory symptoms. Among these 21 patients, 12(57.1%) reported paresthesia, 6(28.6%) reported pain, 3(14.3%) reported both. 2) fifteen(34%) of the 44 patients with antipsychotic-induced EFSs reported sensory symptoms, while only 6(9.5%) of the 63 patients without EFSs reported sensory symptoms(p<0.01). The severity of sensory symptoms was significantly correlated with the EPSs rating score(p=0.001). 3) In the patients with sensory symptoms, the women significantly outnumbered the men(p<0.05). Any risk factor of sensory symptoms, however, couldn't be found in age, diagnosis, and drug. The subjective response including sensory symptoms were associated with drug response, drug compliance, quality of life and prognosis. It is suggested that further systematic investigation and interest about sensory symptoms and subjective response of the acute EPSs should be needed.
Subject(s)
Female , Humans , Antipsychotic Agents , Asian People , Compliance , Cross-Cultural Comparison , Diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Pain Measurement , Paresthesia , Parkinsonian Disorders , Prognosis , Quality of Life , Risk Factors , SensationABSTRACT
The study was designed to evaluate the significant roles of SSRI in rat of depression model. Chronic exposure to mild unpredictable stress has been found to depress the consumption of sweet 1% sucrose solutions in the Sprague-Dawley rats. We applied the variety of 11 types of stress regimens and identified depressive behavious(developed by Willner) in 70 Sprague-Dawley rats. Rats in experiments were stratified into 6 groups, i.e.; 3 kinds of SSRI(paroxetine, fluoxetine, sertraline), clomipramine, choline and saline control. Memory function was evaluated by passive avoidance learning and retention test. The authors determined how long memory retention would remain improved with 24 hour, 1 week, 2 weeks, 3 weeks, and 4 weeks at training-testing interval in depressive states of the Sprague-Dowley rats. The results were as follows; 1) There were to significant differences between the 6 groups at the 24 hour training-testing interval. 2) The paroxetine treated group showed significant differences from the control group at the 1 week and 2 weeks training-testing interval. 3) The paroxetine and the fluoxetine treated groups showed significant differences from the control group at 3 week training-testing interval. 4) The paroxetine and the choline treated groups showed significant differences from the control group 4 week training-testing interval. In summary, paroxetine had on effect on long term memory processing from 1st week to 4th week. Also, fluoxetine(or 3rd week) and choline(at 4th week) had effect on long term memory processing. Sertraline, clomipramine were ineffective on memory processing during 4 weeks observation. Possible explanations why paroxetine had early effect on memory processing than the other selective serotonin reuptake inhibitors are rapid bioavailability, which is the characteristics of pharmacokinetics of paroxetine. In clinical situation, author carefully suggest that SSRI would be beneficial to improve the memory function caused by depressive neurochemical changes.
Subject(s)
Animals , Rats , Avoidance Learning , Biological Availability , Choline , Clomipramine , Depression , Fluoxetine , Memory , Paroxetine , Pharmacokinetics , Rats, Sprague-Dawley , Selective Serotonin Reuptake Inhibitors , Sertraline , SucroseABSTRACT
No abstract available.
Subject(s)
Animals , Rats , Amnesia, Anterograde , Cholinergic Agents , ElectroshockABSTRACT
No abstract available.
Subject(s)
Humans , Anxiety , Depression , Kidney Transplantation , Kidney , Renal DialysisABSTRACT
No abstract available.