Opiate dependence has become one of the most urgent problems of modernsociety. Opiate dependence involves physical and psychical dependence. Although many addicts can bedetoxified, the relapse ratio of 95% in 5 a demo...Opiate dependence has become one of the most urgent problems of modernsociety. Opiate dependence involves physical and psychical dependence. Although many addicts can bedetoxified, the relapse ratio of 95% in 5 a demonstrates that opiate psychical dependence is aproblem more troublesome. It has been reported that acute and chronic administration of L- NNA canmarkedly retard the development of tolerance to physical dependence on morphine, and suppress theabstinence syndromes precipitated by naloxone in opiate dependent rodents, and even reverse theexisting morphine tolerance. However, the effect of L-NNA on the positive reinforcement ofpsychically active substances and its possible mechanism have not yet been reported. In presentstudy, the effect of L- NNA en the psychical dependence induced by opiates was evaluated on thebasis of conditioned place preference.展开更多
The swelling behavior of argillaceous rocks is a complex phenomenon and has been determined using a lot of indexes in the literature. Determining the required modeling indexes that need to be performed requires expens...The swelling behavior of argillaceous rocks is a complex phenomenon and has been determined using a lot of indexes in the literature. Determining the required modeling indexes that need to be performed requires expensive tests and extensive time in different laboratories. In some of the cases, it is too diffi- cult to find a relation between the effective variables and swelling potential. This paper suggests a method for modeling the time dependent swelling pressure of argillaceous rocks. The trend of short term swelling potential during the first 3 days of the swelling pressure testing is used for modeling the long term swelling pressure of mudstone that is recorded during months. The artificial neural network (ANN) as a power tool is used for modeling this nonlinear and complex behavior. This method enables predicting the swelling potential of argillaceous rocks when the required indexes and also correlation between them is unattainable. This method facilitates the model of all studied samples under a unique formulation.展开更多
The activity of Ca2+/calmodulin-dependent protein kinase IV(Ca MKIV) is sensitive to activity-dependent changes in the level of intracellular Ca2+.Following neuronal stimulation,the activation of Ca MKIV may trigger s...The activity of Ca2+/calmodulin-dependent protein kinase IV(Ca MKIV) is sensitive to activity-dependent changes in the level of intracellular Ca2+.Following neuronal stimulation,the activation of Ca MKIV may trigger synaptic modifications and transcriptional responses,both of which are involved in regulating cognitive and emotional behavior.Here,we used Ca MKIV knockout(KO) neurons and mice to examine the function of Ca MKIV in Ca2+-stimulated intracellular signaling and animal behavior,respectively.Following NMDA receptor activation or membrane depolarization,the up-regulation of CREB(c AMP responsive element binding protein) and its target gene Bdnf(brain-derived neurotrophic factor) was intact in cortical neurons obtained from Ca MKIV KO mice.Ca MKIV KO mice displayed severe impairment in contextual fear memory but normal locomotor activity and anxiety level in the contextual training chamber.Although Ca MKIV KO mice showed normal memory in the standard passive avoidance task,they were defective in learning the temporal dissociative passive avoidance task.As indicated by the light/dark test and marble-burying test data,Ca MKIV KO mice showed less anxiety and normal perseveration.In the voluntary wheel-running test,Ca MKIV KO mice showed normal running time and distance but higher maximal running speed.Our results demonstrate the function of Ca MKIV in regulating different forms of fear memory,anxiety,and certain aspect of motor function.展开更多
In statistics and machine learning communities, the last fifteen years have witnessed a surge of high-dimensional models backed by penalized methods and other state-of-the-art variable selection techniques.The high-di...In statistics and machine learning communities, the last fifteen years have witnessed a surge of high-dimensional models backed by penalized methods and other state-of-the-art variable selection techniques.The high-dimensional models we refer to differ from conventional models in that the number of all parameters p and number of significant parameters s are both allowed to grow with the sample size T. When the field-specific knowledge is preliminary and in view of recent and potential affluence of data from genetics, finance and on-line social networks, etc., such(s, T, p)-triply diverging models enjoy ultimate flexibility in terms of modeling, and they can be used as a data-guided first step of investigation. However, model selection consistency and other theoretical properties were addressed only for independent data, leaving time series largely uncovered. On a simple linear regression model endowed with a weakly dependent sequence, this paper applies a penalized least squares(PLS) approach. Under regularity conditions, we show sign consistency, derive finite sample bound with high probability for estimation error, and prove that PLS estimate is consistent in L_2 norm with rate (s log s/T)~1/2.展开更多
Objective: This present study is to investigate the biochemical adaptations in the rdated brain regions of the mesolimbic dopamine system, such as the ventral tegmental area (VFA), nucleus accumbens (NAc), amygda...Objective: This present study is to investigate the biochemical adaptations in the rdated brain regions of the mesolimbic dopamine system, such as the ventral tegmental area (VFA), nucleus accumbens (NAc), amygdale (Amy), prefrontal cortex (PFC) , substantia nigra (SN) and caudateputamen (CPu) in response to heroin self-administration in rats and observe the effect of electroacupuncture on them. Methods. Thirty rats were trained by nose-poking response to establish stable intravenous heroin self-administration within 14 days, and then divided randomly into model group (group B) including 6 rats, withdrawal group which were withdrawn from heroin for 1 week (group C, n = 6) and for 2 weeks (group D, n= 6), during which time they only lived in their individual home cages, and dectrtyacupuncture group which were also withdrawn from heroin for 1 week (group E, n= 6) and for 2 weeks (group F, n = 6), during which time they were given electro-acupuncture treatment for 20 min daily and then returned to their individual home cages; in the meantime, another 6 rats were trained by nose-poking response with saline for 14 days as control (group A); Then the leeds of tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) in VFA, NAc, Amy, PFC, SN, CPu were detected with immunohistochemistry method. Results. The leeds of TH and GFAP in VFA of the heroin self administrating rats were obviously increased, and the leeds of TH and GFAP in NAc were also decreased, and these changes were not found in SN, CPu, Amy and PFC; Electro-acupuncture could promote the up regulation of TH and GFAP in VTA and down-regulation of TH and GFAP in NAc to return to the normal leeel. Conclusions: The chronic heroin self administration produced some biochemical adaptations in the related brain regions of the mesolimbic dopamine system and electroacupuncture could promote the repair of the "injured" DA neurons in VTA of heroin addicted rats and their functional recovery.展开更多
In the presence of glutamate and co-agonists, e.g., glycine, the N-methyl-D-aspartate receptor (NMDAR) plays an important role in physiological and pathophysiological brain processes. Previous studies indicate glyci...In the presence of glutamate and co-agonists, e.g., glycine, the N-methyl-D-aspartate receptor (NMDAR) plays an important role in physiological and pathophysiological brain processes. Previous studies indicate glycine could inhibit NMDAR respons- es induced by high concentration of NMDA in hippocampal neurons. The mechanism underlying this inhibitory impact, how- ever, has been unclear. In this study, the whole-cell patch-clamp recording and Ca2+ imaging with Fluo-3/AM under laser scanning confocal microscope were used to analyze the possible involvement of NMDAR subnnits in this effect. We found that the peak current of NMDARs and Ca2+ influx induced by high concentration of NMDA were reduced by treatment of gly- cine (0.03-10 I.tmol L-1) in a dose-dependent manner, and that the glycine-dependent inhibition of NMDAR responses, which were induced at 300 mol L-1 NMDA, was reversed by ZnCI2 through the blocking of the NR2A subunit of NMDARs, but was less influenced by ifenprodil, a NR2B inhibitor. Our results suggest that the glycine-dependent inactivation of NMDARs is potentially modulated by the regulatory subunit NR2A.展开更多
基金ThisprojectwassupportedbyGrantofthePLALaboratoryforNewDrugEvaluation (No .96-0 2 )
文摘Opiate dependence has become one of the most urgent problems of modernsociety. Opiate dependence involves physical and psychical dependence. Although many addicts can bedetoxified, the relapse ratio of 95% in 5 a demonstrates that opiate psychical dependence is aproblem more troublesome. It has been reported that acute and chronic administration of L- NNA canmarkedly retard the development of tolerance to physical dependence on morphine, and suppress theabstinence syndromes precipitated by naloxone in opiate dependent rodents, and even reverse theexisting morphine tolerance. However, the effect of L-NNA on the positive reinforcement ofpsychically active substances and its possible mechanism have not yet been reported. In presentstudy, the effect of L- NNA en the psychical dependence induced by opiates was evaluated on thebasis of conditioned place preference.
文摘The swelling behavior of argillaceous rocks is a complex phenomenon and has been determined using a lot of indexes in the literature. Determining the required modeling indexes that need to be performed requires expensive tests and extensive time in different laboratories. In some of the cases, it is too diffi- cult to find a relation between the effective variables and swelling potential. This paper suggests a method for modeling the time dependent swelling pressure of argillaceous rocks. The trend of short term swelling potential during the first 3 days of the swelling pressure testing is used for modeling the long term swelling pressure of mudstone that is recorded during months. The artificial neural network (ANN) as a power tool is used for modeling this nonlinear and complex behavior. This method enables predicting the swelling potential of argillaceous rocks when the required indexes and also correlation between them is unattainable. This method facilitates the model of all studied samples under a unique formulation.
基金supported by US National Institutes of Health grant(MH076906)to Wang Hong Bing
文摘The activity of Ca2+/calmodulin-dependent protein kinase IV(Ca MKIV) is sensitive to activity-dependent changes in the level of intracellular Ca2+.Following neuronal stimulation,the activation of Ca MKIV may trigger synaptic modifications and transcriptional responses,both of which are involved in regulating cognitive and emotional behavior.Here,we used Ca MKIV knockout(KO) neurons and mice to examine the function of Ca MKIV in Ca2+-stimulated intracellular signaling and animal behavior,respectively.Following NMDA receptor activation or membrane depolarization,the up-regulation of CREB(c AMP responsive element binding protein) and its target gene Bdnf(brain-derived neurotrophic factor) was intact in cortical neurons obtained from Ca MKIV KO mice.Ca MKIV KO mice displayed severe impairment in contextual fear memory but normal locomotor activity and anxiety level in the contextual training chamber.Although Ca MKIV KO mice showed normal memory in the standard passive avoidance task,they were defective in learning the temporal dissociative passive avoidance task.As indicated by the light/dark test and marble-burying test data,Ca MKIV KO mice showed less anxiety and normal perseveration.In the voluntary wheel-running test,Ca MKIV KO mice showed normal running time and distance but higher maximal running speed.Our results demonstrate the function of Ca MKIV in regulating different forms of fear memory,anxiety,and certain aspect of motor function.
基金supported by Natural Science Foundation of USA (Grant Nos. DMS1206464 and DMS1613338)National Institutes of Health of USA (Grant Nos. R01GM072611, R01GM100474 and R01GM120507)
文摘In statistics and machine learning communities, the last fifteen years have witnessed a surge of high-dimensional models backed by penalized methods and other state-of-the-art variable selection techniques.The high-dimensional models we refer to differ from conventional models in that the number of all parameters p and number of significant parameters s are both allowed to grow with the sample size T. When the field-specific knowledge is preliminary and in view of recent and potential affluence of data from genetics, finance and on-line social networks, etc., such(s, T, p)-triply diverging models enjoy ultimate flexibility in terms of modeling, and they can be used as a data-guided first step of investigation. However, model selection consistency and other theoretical properties were addressed only for independent data, leaving time series largely uncovered. On a simple linear regression model endowed with a weakly dependent sequence, this paper applies a penalized least squares(PLS) approach. Under regularity conditions, we show sign consistency, derive finite sample bound with high probability for estimation error, and prove that PLS estimate is consistent in L_2 norm with rate (s log s/T)~1/2.
基金Supported by the National Nature Science Foundation(30271637)the State Administration of TCM(02-03LQ05)
文摘Objective: This present study is to investigate the biochemical adaptations in the rdated brain regions of the mesolimbic dopamine system, such as the ventral tegmental area (VFA), nucleus accumbens (NAc), amygdale (Amy), prefrontal cortex (PFC) , substantia nigra (SN) and caudateputamen (CPu) in response to heroin self-administration in rats and observe the effect of electroacupuncture on them. Methods. Thirty rats were trained by nose-poking response to establish stable intravenous heroin self-administration within 14 days, and then divided randomly into model group (group B) including 6 rats, withdrawal group which were withdrawn from heroin for 1 week (group C, n = 6) and for 2 weeks (group D, n= 6), during which time they only lived in their individual home cages, and dectrtyacupuncture group which were also withdrawn from heroin for 1 week (group E, n= 6) and for 2 weeks (group F, n = 6), during which time they were given electro-acupuncture treatment for 20 min daily and then returned to their individual home cages; in the meantime, another 6 rats were trained by nose-poking response with saline for 14 days as control (group A); Then the leeds of tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) in VFA, NAc, Amy, PFC, SN, CPu were detected with immunohistochemistry method. Results. The leeds of TH and GFAP in VFA of the heroin self administrating rats were obviously increased, and the leeds of TH and GFAP in NAc were also decreased, and these changes were not found in SN, CPu, Amy and PFC; Electro-acupuncture could promote the up regulation of TH and GFAP in VTA and down-regulation of TH and GFAP in NAc to return to the normal leeel. Conclusions: The chronic heroin self administration produced some biochemical adaptations in the related brain regions of the mesolimbic dopamine system and electroacupuncture could promote the repair of the "injured" DA neurons in VTA of heroin addicted rats and their functional recovery.
基金supported by the National Basic Research Program of China (Grant No. J20110170)the National Natural Science Foundation of China (Grant Nos. 81000497 and 81071614)
文摘In the presence of glutamate and co-agonists, e.g., glycine, the N-methyl-D-aspartate receptor (NMDAR) plays an important role in physiological and pathophysiological brain processes. Previous studies indicate glycine could inhibit NMDAR respons- es induced by high concentration of NMDA in hippocampal neurons. The mechanism underlying this inhibitory impact, how- ever, has been unclear. In this study, the whole-cell patch-clamp recording and Ca2+ imaging with Fluo-3/AM under laser scanning confocal microscope were used to analyze the possible involvement of NMDAR subnnits in this effect. We found that the peak current of NMDARs and Ca2+ influx induced by high concentration of NMDA were reduced by treatment of gly- cine (0.03-10 I.tmol L-1) in a dose-dependent manner, and that the glycine-dependent inhibition of NMDAR responses, which were induced at 300 mol L-1 NMDA, was reversed by ZnCI2 through the blocking of the NR2A subunit of NMDARs, but was less influenced by ifenprodil, a NR2B inhibitor. Our results suggest that the glycine-dependent inactivation of NMDARs is potentially modulated by the regulatory subunit NR2A.