Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to m...Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning. Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.展开更多
The social transmission of food preferences(STFP) is a behavioural task of olfactory memory, in which an observer rat learns safe food odours from a demonstrator rat, and shows preference for this odour in a subsequen...The social transmission of food preferences(STFP) is a behavioural task of olfactory memory, in which an observer rat learns safe food odours from a demonstrator rat, and shows preference for this odour in a subsequent choice test. However, previous studies have failed to detect the transmission of information about food of potential danger and food aversion using STFP test. In this study, we tested how demonstrators' health affects the exchange of odour information and whether observers can learn danger information from an unhealthy demonstrator. As expected, the observer rat formed an odour preference after interacting with a demonstrator rat that had just eaten food containing a new odour, however, odour preference rather than aversion was also formed after interacting with a demonstrator rat injected with LiCl(used to induce gastric malaise). Furthermore, anaesthetized demonstrator rats and half-anaesthetized demonstrator rats, which showed obvious motor deficits suggesting an unhealthy state, also socially transmitted food preferences to observers. These results suggest that the social transmission of food preferences task is independent of a demonstrators' health, and that information about dangerous foods cannot be transmitted using this behavioural task.展开更多
DEAR EDITOR,Cognitive flexibility is crucial for animal survival but is frequently impaired in neuropsychiatric disorders.Although many brain structures and functional networks are involved in cognitive flexibility,th...DEAR EDITOR,Cognitive flexibility is crucial for animal survival but is frequently impaired in neuropsychiatric disorders.Although many brain structures and functional networks are involved in cognitive flexibility,the neural mechanisms underlying cooperation among specific functional networks remain unclear from a global perspective.In this study,[^(18)F]-fluorodeoxyglucose positron emission tomography(FDG-PET)was performed on 19 male tree shrews after four different visual discrimination tasks,including baseline,learning expert(LE),reversal naive(RN),and reversal expert(RE).展开更多
Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of fe...Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 °C, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.展开更多
Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feed...Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy.Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases.However,basal physiological indexes of tree shrew,especially those related to human disease,have not been systematically reported.Accordingly,we established important basal physiological indexes of domesticated tree shrews including several factors:(1)body weight,(2)core body temperature and rhythm,(3)diet metabolism,(4)locomotor rhythm,(5)electroencephalogram,(6)glycometabolism and(7)serum and urinary hormone level and urinary cortisol rhythm.We compared the physiological parameters of domesticated tree shrew with that of rats and macaques.Results showed that(a)the core body temperature of the tree shrew was 39.59±0.05°C,which was higher than that of rats and macaques;(b)Compared with wild tree shrews,with two activity peaks,domesticated tree shrews had only one activity peak from 17:30 to 19:30;(c)Compared with rats,tree shrews had poor carbohydrate metabolism ability;and(d)Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews,which matched activity peaks in wild tree shrews.These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.展开更多
Substance use disorder remains a major challenge,with an enduring need to identify and evaluate new,translational targets for effective treatment.Here,we report the upregulation of Hypoxia-inducible factor-1α(HIF-1α...Substance use disorder remains a major challenge,with an enduring need to identify and evaluate new,translational targets for effective treatment.Here,we report the upregulation of Hypoxia-inducible factor-1α(HIF-1α)expression by roxadustat(Rox),a drug developed for renal anemia that inhibits HIF prolyl hydroxylase to prevent degradation of HIF-1α,administered either systemically or locally into selected brain regions,suppressed morphine(Mor)-induced conditioned place preference(CPP).展开更多
Synaptic dysfunction is a core component of the pathophysiology of schizophrenia.However,the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood.The Stonin 2(ST...Synaptic dysfunction is a core component of the pathophysiology of schizophrenia.However,the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood.The Stonin 2(STON2)gene encodes a major adaptor for clathrin-mediated endocytosis(CME)of synaptic vesicles.In this study,we showed that the C-C(307Pro-851Ala)haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of CME.We found that schizophrenia-related STON2 variations led to protein dephosphorylation,which affected its interaction with synaptotagmin 1(Syt1),a calcium sensor protein located in the presynaptic membrane that is critical for CME.STON2307Pro851Ala knockin mice exhibited deficits in synaptic transmission,short-term plasticity,and schizophrenia-like behaviors.Moreover,among seven antipsychotic drugs,patients with the C-C(307Pro-851Ala)haplotype responded better to haloperidol than did the T-A(307Ser-851Ser)carriers.The recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2307Pro851Ala knockin mice.Our findings demonstrated the effect of schizophreniarelated STON2 variations on synaptic dysfunction through the regulation of CME,which might be attractive therapeutic targets for treating schizophrenia-like phenotypes.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China (No. 30470549)the National Basic Research Priorities Programme (973) of China (No.2006CBS00800)
文摘Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning. Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.
基金supported by the 973 Program of the Ministry of Science and Technology of China(2013CB835103)the Strategic Priority Research Program of Chinese Academy of Science(XDB02020200)the National Science Foundation of China(31100775)
文摘The social transmission of food preferences(STFP) is a behavioural task of olfactory memory, in which an observer rat learns safe food odours from a demonstrator rat, and shows preference for this odour in a subsequent choice test. However, previous studies have failed to detect the transmission of information about food of potential danger and food aversion using STFP test. In this study, we tested how demonstrators' health affects the exchange of odour information and whether observers can learn danger information from an unhealthy demonstrator. As expected, the observer rat formed an odour preference after interacting with a demonstrator rat that had just eaten food containing a new odour, however, odour preference rather than aversion was also formed after interacting with a demonstrator rat injected with LiCl(used to induce gastric malaise). Furthermore, anaesthetized demonstrator rats and half-anaesthetized demonstrator rats, which showed obvious motor deficits suggesting an unhealthy state, also socially transmitted food preferences to observers. These results suggest that the social transmission of food preferences task is independent of a demonstrators' health, and that information about dangerous foods cannot be transmitted using this behavioural task.
基金supported by the National Natural Science Foundation of China(11975249,81771923,12175268,32071029,31861143037)China Postdoctoral Science Foundation(2021T140668)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32020000)。
文摘DEAR EDITOR,Cognitive flexibility is crucial for animal survival but is frequently impaired in neuropsychiatric disorders.Although many brain structures and functional networks are involved in cognitive flexibility,the neural mechanisms underlying cooperation among specific functional networks remain unclear from a global perspective.In this study,[^(18)F]-fluorodeoxyglucose positron emission tomography(FDG-PET)was performed on 19 male tree shrews after four different visual discrimination tasks,including baseline,learning expert(LE),reversal naive(RN),and reversal expert(RE).
基金supported by grants from the Chinese Academy of Sciences (KSCX2-EW-R-12, KSCX2-EW-J-23)the National Natural Science Foundation of China (81171294)Shanghai Science & Technology Development Foundation(12140904200)
文摘Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 °C, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.
基金This work was supported by grants from the Chinese Academy of Sciences(KSCX2-EW-R-12,KSCX2-EW-J-23)the National Natural Science Foundation of China(81171294)Shanghai Science&Technology Development Foundation(12140904200).
文摘Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy.Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases.However,basal physiological indexes of tree shrew,especially those related to human disease,have not been systematically reported.Accordingly,we established important basal physiological indexes of domesticated tree shrews including several factors:(1)body weight,(2)core body temperature and rhythm,(3)diet metabolism,(4)locomotor rhythm,(5)electroencephalogram,(6)glycometabolism and(7)serum and urinary hormone level and urinary cortisol rhythm.We compared the physiological parameters of domesticated tree shrew with that of rats and macaques.Results showed that(a)the core body temperature of the tree shrew was 39.59±0.05°C,which was higher than that of rats and macaques;(b)Compared with wild tree shrews,with two activity peaks,domesticated tree shrews had only one activity peak from 17:30 to 19:30;(c)Compared with rats,tree shrews had poor carbohydrate metabolism ability;and(d)Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews,which matched activity peaks in wild tree shrews.These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.
基金This research was funded by the National Innovation of Science and Technology-2030(Program of Brain Science and Brain-lnspired Intelligence Technology)Grant(2021ZD0204004)the National Natural Science Foundation of China(81973334,81773702)。
文摘Substance use disorder remains a major challenge,with an enduring need to identify and evaluate new,translational targets for effective treatment.Here,we report the upregulation of Hypoxia-inducible factor-1α(HIF-1α)expression by roxadustat(Rox),a drug developed for renal anemia that inhibits HIF prolyl hydroxylase to prevent degradation of HIF-1α,administered either systemically or locally into selected brain regions,suppressed morphine(Mor)-induced conditioned place preference(CPP).
基金supported by the Key Realm R&D Program of Guangdong Province(2019B030335001)the National Natural Science Foundation of China(82330042,81825009,82071541,81971283,82271576,and 82101570)+2 种基金Changping Laboratory(2021B-01-01)the China Postdoctoral Science Foundation(2021M690421)the Non-profit Central Research Institute Chinese Academy of Medical Sciences(2023-PT320-08).
文摘Synaptic dysfunction is a core component of the pathophysiology of schizophrenia.However,the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood.The Stonin 2(STON2)gene encodes a major adaptor for clathrin-mediated endocytosis(CME)of synaptic vesicles.In this study,we showed that the C-C(307Pro-851Ala)haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of CME.We found that schizophrenia-related STON2 variations led to protein dephosphorylation,which affected its interaction with synaptotagmin 1(Syt1),a calcium sensor protein located in the presynaptic membrane that is critical for CME.STON2307Pro851Ala knockin mice exhibited deficits in synaptic transmission,short-term plasticity,and schizophrenia-like behaviors.Moreover,among seven antipsychotic drugs,patients with the C-C(307Pro-851Ala)haplotype responded better to haloperidol than did the T-A(307Ser-851Ser)carriers.The recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2307Pro851Ala knockin mice.Our findings demonstrated the effect of schizophreniarelated STON2 variations on synaptic dysfunction through the regulation of CME,which might be attractive therapeutic targets for treating schizophrenia-like phenotypes.