RESUMEN
OBJECTIVE@#To study the effects of ketamine and alcohol on learning and memory in mice and its possible mechanism.@*METHODS@#Forty mice were divided into 4 groups: normal control group, ketamine group, alcohol group, and alcohol plus ketamine group. Ketamine and alcohol were given by intraperitoneal injection and intragastric administration, respectively, 1 time per day, for 14 days. The ability of learning and memory in mice was tested by the method of step-down and Morris water maze. Acetylcholine (ACh) and 5-hydroxy tryptamine(5-HT) in mice brain tissue were analyzed for the possible mechanism.@*RESULTS@#(1) Step-down: The treatment groups lessened the latency and added wrong times (P < 0.05). The number of errors in the combined treatment group significantly increased comparing with the single drug treatment group (P < 0.05). (2) Morris water-maze: The treatment groups prolonged the latency (P < 0.05), reduced the target quadrant activity time significantly (P < 0.05), and decreased the numbers of crossing the former platform significantly (P < 0.05). (3) Biochemical index determination: The concentrations of ACh and 5-HT in treatment groups decreased significantly (P < 0.05), showed a more decreasement comparing with the single drug treatment group.@*CONCLUSION@#Ketamine has a synergistic effect with alcohol on learning and memory impairment in mice, which may be related to the common inhibitive effect on the ACh and 5-HT.
Asunto(s)
Animales , Masculino , Ratones , Acetilcolina/metabolismo , Alcoholes/farmacología , Encéfalo/fisiopatología , Sinergismo Farmacológico , Ketamina/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Trastornos de la Memoria/fisiopatología , Ratones Endogámicos ICR , Serotonina/metabolismo , Conducta Espacial/efectos de los fármacosRESUMEN
OBJECTIVE@#To explore the effect of ketamine on adrenal pheochromocytoma (PC12) cell proliferation inhibition and induction of apoptosis and its mechanism.@*METHODS@#PC12 cells of rats were models for dopaminergic neuron. PC12 cells were cultured with ketamine at concentrations of 0.9, 1.2, 1.5, 1.8 and 2.1 mmol/L, respectively. The cell viability was measured by MTT method after incubation at 12, 24, 48 and 72h. Hoechst stain was used to observe the morphological changes of apoptosis. PC12 cells cultured after 48 h with different concentrations of ketamine were selected to detect apoptotic rate using flow cytometry and detect the expression of bax and bcl-2 proteins using Western blotting.@*RESULTS@#For different concentrations of ketamine, vitality of PC12 cells significantly decreased with increase of the incubation time. Apoptosis was obviously observed using Hoechst staining. Flow cytometry showed that apoptosis rates significantly increased with increasing ketamine concentrations.@*CONCLUSION@#Ketamine can inhibit the proliferation of PC12 cell by inducing apoptosis of the PC12 cell in a concentrations-dependent manner. The underlying mechanism may be related to promoting the expression of bax and inhibiting the expression of bcl-2 in the cells.
Asunto(s)
Animales , Ratas , Anestésicos Disociativos/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Regulación de la Expresión Génica/efectos de los fármacos , Ketamina/farmacología , Células PC12 , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factores de Tiempo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVE@#To observe the symptoms similar to schizophrenia in mice after ketamine single or continuous injection and to evaluate the feasibility of schizophrenia model injected with different dose of ketamine.@*METHODS@#A total of 40 male mice were randomly divided into 4 groups, which were injected intraperitoneally with physiological saline (control group), 25 mg/kg ketamine (low dose group), 50 mg/kg ketamine (middle dose group), and 100 mg/kg ketamine (high dose group) qd for 7 days continuously. The behavior changes of mice were observed.@*RESULTS@#Hyperactivity, stereotyped behavior and ataxia (P < 0.01) were observed in high dose group after single injection. After continuous injection of ketamine for 7 days, the middle dose group showed hyperactivity, stereotyped behavior and ataxia (P < 0.05), stereotyped behavior and ataxia were more significant in high dose group (P < 0.01).@*CONCLUSION@#Ketamine can induce the symptoms similar to schizophrenia in mice after single or continuous injection. The symptoms induced by high dose ketamine will be more prominent and stable after continuous injection.
Asunto(s)
Animales , Masculino , Ratones , Ataxia/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Psiquiatría Forense , Inyecciones Intraperitoneales , Ketamina/administración & dosificación , Actividad Motora/efectos de los fármacos , Distribución Aleatoria , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Esquizofrenia/patología , Conducta Estereotipada/efectos de los fármacosRESUMEN
OBJECTIVE@#To explore the correlation between signs similar to schizophrenia in mice after ketamine administration and the expressions of NRG1 and ErbB4 mRNA in order to explain the possible pathogenesis of schizophrenia.@*METHODS@#Fifty KM mice were randomly divided into 5 groups which were administered intraperitoneally with saline, clozapine and different dosages ketamine. The ketamine groups were administered intraperitoneally with low dosage (25 mg/kg), middle dosage (50 mg/kg) and high dosage (100 mg/kg) one time every day for 7 days. After administration of 100 mg/kg ketamine for 7 days, the clozapine group was introgastrically administered 20 mg/kg with clozapine one time every day for 7 days. The pathological changes of hippocampus neurons were observed by HE stain. The expressions of the NRG1 and ErbB4 mRNA in hippocampus were detected by reverse transcriptase polymerase chain reaction (RT-PCR).@*RESULTS@#In the group with high dosage of ketamine, the levels of NRG1 and ErbB4 mRNA were significantly lower than that of the group with saline.@*CONCLUSION@#Ketamine may induce signs similar to schizophrenia in KM mice. The mechanism may be involved in the reduction of NRG1 and ErbB4 mRNA expression.