The evaluation of personality traits is important for the better understanding of the person suffering from psychosis and for treatment individualization. However literature on patients' personality and character ...The evaluation of personality traits is important for the better understanding of the person suffering from psychosis and for treatment individualization. However literature on patients' personality and character in such disorders is limited. The aim of this review was to summarize the literature on sensation/novelty seeking(SNS), a trait which is biologically based and highly heritable and is associated with dopamine activity, and refers to a person's tendency to seek varied, novel, complex, and intense sensations and experiences. A total of 38 studies were included in this review, involving 2808 patients and 2039 healthy controls. There is consistent evidence that this trait is independentlyassociated with alcohol and substance abuse in patients with schizophrenia and related disorders. The estimation of SNS would help clinicians to identify patients at risk for abuse. There is also some evidence that higher SNS levels may relate to medication non-adherence and seem to increase the risk of patients' aggressive and violent behavior, but studies are scarce. SNS was found not to be related to suicidality, whereas in the fields of patients' quality of life and psychopathology results are contradictory, but most studies show no possible association. Several studies suggest that SNS is lower in psychotic patients compared to controls, whereas most yield no differences. The evidence for this trait as a potential endophenotype of schizophrenia is weak. SNS may be implicated in psychotic disorders' course and prognosis in several ways and should be always inquired for. This trait can be reliably measured with the use of easily applicable self-rated instruments, and patients' accounts could inform clinicians when planning management and delivering individualized treatment.展开更多
Abnormal approach-avoidance behavior has been linked to deficits in the mesolimbic dopamine(DA)system of the brain. Recently, increasing evidence has indicated that toll-like receptor 4(TLR4), an important pattern...Abnormal approach-avoidance behavior has been linked to deficits in the mesolimbic dopamine(DA)system of the brain. Recently, increasing evidence has indicated that toll-like receptor 4(TLR4), an important pattern-recognition receptor in the innate immune system,can be directly activated by substances of abuse, resulting in an increase of the extracellular DA level in the nucleus accumbens. We thus hypothesized that TLR4-dependent signaling might regulate approach-avoidance behavior. To test this hypothesis, we compared the novelty-seeking and social interaction behaviors of TLR4-deficient(TLR4^(-/-))and wild-type(WT) mice in an approach-avoidance conflict situation in which the positive motivation to explore a novel object or interact with an unfamiliar mouse was counteracted by the negative motivation to hide in exposed,large spaces. We found that TLR4^(-/-)mice exhibitedreduced novelty-seeking and social interaction in the large open spaces. In less stressful test apparatuses similar in size to the mouse cage, however, TLR4^(-/-)mice performed normally in both novelty-seeking and social interaction tests. The reduced exploratory behaviors under approachavoidance conflict were not due to a high anxiety level or an enhanced fear response in the TLR4^(-/-)mice, as these mice showed normal anxiety and fear responses in the open field and passive avoidance tests, respectively. Importantly,the novelty-seeking behavior in the large open field induced a higher level of c-Fos activation in the nucleus accumbens shell(NAc Sh) in TLR4^(-/-)mice than in WT mice. Partially inactivating the NAc Sh via infusion of GABA receptor agonists restored the novelty-seeking behavior of TLR4^(-/-)mice. These data suggested that TLR4 is crucial for positive motivational behavior under approach-avoidance conflict. TLR4-dependent activation of neurons in the NAc Sh may contribute to this phenomenon.展开更多
The Roman high(RHA) and low-Avoidance (RLA) rats were selectively bred for rapid vs poor acquisition of two-way active avoidance behavior. These lines differ in numerous behavioral traits, with RLA rats being more fea...The Roman high(RHA) and low-Avoidance (RLA) rats were selectively bred for rapid vs poor acquisition of two-way active avoidance behavior. These lines differ in numerous behavioral traits, with RLA rats being more fearful/anxious than RHA rats, and the latter being novelty-seekers and showing larger intake of, and preference for, addictive substances including ethanol (ETH). Moreover, several differences in central dopaminergic, serotonergic, and GABAergic functions have been reported in these two lines. Since those neural systems are involved in the regulation of ETH consumption, it was considered of interest to investigate: 1) the differences in ETH intake and preference between RHA and RLA rats, 2) the effects of ETH on DA release in the shell of the nucleus accumbens (AcbSh) using brain microdialysis. ETH solutions of increasing concentrations (2% - 10%) were presented on alternate days in a free choice with water. To examine ETH intake and preference stability, animals were subsequently switched to daily presentations of 10% ETH for 10 consecutive days. RHA rats consumed significantly larger amounts of ETH and displayed higher ETH preference than did RLA rats throughout the acquisition and maintenance phases. Following chronic exposure to ETH the animals were habituated to a restricted access to ETH schedule (2% ETH, 2 h per day × 4 days) before surgical implantation of a dialysis probe in the AcbSh. Under these experimental conditions, voluntary ETH intake (2%, 1 h, p.o.) produced a significant increase in accumbal DA output in RHA rats but not in their RLA counterparts. Finally, the i.p. administration of ETH (0.25 g/kg) to na?ve Roman rats produced a significant increment in accumbal DA output only in RHA rats. These results indicate that the mesolimbic dopaminergic system of RHA rats is more responsive to the effects of ETH than that of RLA rats.展开更多
文摘The evaluation of personality traits is important for the better understanding of the person suffering from psychosis and for treatment individualization. However literature on patients' personality and character in such disorders is limited. The aim of this review was to summarize the literature on sensation/novelty seeking(SNS), a trait which is biologically based and highly heritable and is associated with dopamine activity, and refers to a person's tendency to seek varied, novel, complex, and intense sensations and experiences. A total of 38 studies were included in this review, involving 2808 patients and 2039 healthy controls. There is consistent evidence that this trait is independentlyassociated with alcohol and substance abuse in patients with schizophrenia and related disorders. The estimation of SNS would help clinicians to identify patients at risk for abuse. There is also some evidence that higher SNS levels may relate to medication non-adherence and seem to increase the risk of patients' aggressive and violent behavior, but studies are scarce. SNS was found not to be related to suicidality, whereas in the fields of patients' quality of life and psychopathology results are contradictory, but most studies show no possible association. Several studies suggest that SNS is lower in psychotic patients compared to controls, whereas most yield no differences. The evidence for this trait as a potential endophenotype of schizophrenia is weak. SNS may be implicated in psychotic disorders' course and prognosis in several ways and should be always inquired for. This trait can be reliably measured with the use of easily applicable self-rated instruments, and patients' accounts could inform clinicians when planning management and delivering individualized treatment.
基金supported by the National Basic Research Development Program(973 Program)of China(2013CB530902)the National Natural Science Foundation of China(91132712,81571125,81221003 and 81300979)+2 种基金the Natural Science Foundation of Zhejiang Province,China(LR12C09001 and Q13C090002)the Fundamental Research Funds for the Central Universities of China(2014FZA7008)partly supported by a Chinese Postdoctoral Science Foundation grant(2015M570501)
文摘Abnormal approach-avoidance behavior has been linked to deficits in the mesolimbic dopamine(DA)system of the brain. Recently, increasing evidence has indicated that toll-like receptor 4(TLR4), an important pattern-recognition receptor in the innate immune system,can be directly activated by substances of abuse, resulting in an increase of the extracellular DA level in the nucleus accumbens. We thus hypothesized that TLR4-dependent signaling might regulate approach-avoidance behavior. To test this hypothesis, we compared the novelty-seeking and social interaction behaviors of TLR4-deficient(TLR4^(-/-))and wild-type(WT) mice in an approach-avoidance conflict situation in which the positive motivation to explore a novel object or interact with an unfamiliar mouse was counteracted by the negative motivation to hide in exposed,large spaces. We found that TLR4^(-/-)mice exhibitedreduced novelty-seeking and social interaction in the large open spaces. In less stressful test apparatuses similar in size to the mouse cage, however, TLR4^(-/-)mice performed normally in both novelty-seeking and social interaction tests. The reduced exploratory behaviors under approachavoidance conflict were not due to a high anxiety level or an enhanced fear response in the TLR4^(-/-)mice, as these mice showed normal anxiety and fear responses in the open field and passive avoidance tests, respectively. Importantly,the novelty-seeking behavior in the large open field induced a higher level of c-Fos activation in the nucleus accumbens shell(NAc Sh) in TLR4^(-/-)mice than in WT mice. Partially inactivating the NAc Sh via infusion of GABA receptor agonists restored the novelty-seeking behavior of TLR4^(-/-)mice. These data suggested that TLR4 is crucial for positive motivational behavior under approach-avoidance conflict. TLR4-dependent activation of neurons in the NAc Sh may contribute to this phenomenon.
文摘The Roman high(RHA) and low-Avoidance (RLA) rats were selectively bred for rapid vs poor acquisition of two-way active avoidance behavior. These lines differ in numerous behavioral traits, with RLA rats being more fearful/anxious than RHA rats, and the latter being novelty-seekers and showing larger intake of, and preference for, addictive substances including ethanol (ETH). Moreover, several differences in central dopaminergic, serotonergic, and GABAergic functions have been reported in these two lines. Since those neural systems are involved in the regulation of ETH consumption, it was considered of interest to investigate: 1) the differences in ETH intake and preference between RHA and RLA rats, 2) the effects of ETH on DA release in the shell of the nucleus accumbens (AcbSh) using brain microdialysis. ETH solutions of increasing concentrations (2% - 10%) were presented on alternate days in a free choice with water. To examine ETH intake and preference stability, animals were subsequently switched to daily presentations of 10% ETH for 10 consecutive days. RHA rats consumed significantly larger amounts of ETH and displayed higher ETH preference than did RLA rats throughout the acquisition and maintenance phases. Following chronic exposure to ETH the animals were habituated to a restricted access to ETH schedule (2% ETH, 2 h per day × 4 days) before surgical implantation of a dialysis probe in the AcbSh. Under these experimental conditions, voluntary ETH intake (2%, 1 h, p.o.) produced a significant increase in accumbal DA output in RHA rats but not in their RLA counterparts. Finally, the i.p. administration of ETH (0.25 g/kg) to na?ve Roman rats produced a significant increment in accumbal DA output only in RHA rats. These results indicate that the mesolimbic dopaminergic system of RHA rats is more responsive to the effects of ETH than that of RLA rats.