大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

目的 探讨吗啡条件性位置偏爱(CPP)不同易感性的大鼠脑伏隔核多巴胺D2受体(D2R)和多巴胺转运体(DAT)水平.方法 将160只雄性Sprague-Dawley大鼠随机抽取30只作为对照组,余130只为吗啡组.对吗啡组在预测试后建立吗啡CPP模型.根据CPP值[以末次CPP测评时大鼠在伴药侧(大鼠注射吗啡后放入该侧,吗啡剂量从5 mg·kg-1·次-1开始逐渐增加,第10天为50 mg·kg-1·次-1)的停留时间减去预测试在该侧停留的时间]将吗啡组大鼠按比例分为高(26只)、中(78只)、低偏爱组(26只),其中高、低偏爱组(每组大鼠死亡各2只)分别于吗啡末次注射(对照组注射『司体积生理盐水)后3 h.3 d和14 d分别处死大鼠(每组各8只),用原位杂交法检测伏隔核D2R和DAT的灰度值(阳性区域的强弱与灰度值呈反比),并与对照组比较.结果 (1)预测试3组CPP值的差异无统计学意义(P>0.05);但在吗啡注射后3 h、戒断后3 d和14 d,高偏爱组CPP值[分别为(507±108)s、(524±113)s、(483±60)s]均长于低偏爱组[分别为(100±74)s、(166±86)s、(149±89)s;P=0.000]和对照组[分别为(97 ±111)s、(39±26)s、(-4.9 ±140.1)s;P=0.000].(2)上述各时点高偏爱组D2R mRNA灰度值(131 ±3、122±5、119±5)均高于低偏爱组(125±4、117±8、114±5)和对照组(11l±6、107±7、106±3;P<0.01);高偏爱组DAT mRNA灰度值(161±5、143±4、134±6)亦高于低偏爱组(156±5、139±3、130±4)和对照组(120±4、126±7、129±4;P<0.01).结论 大鼠吗啡CPP易感性高可能与伏隔核的D2R及DAT表达低下有关.     

四氢原小檗碱对吗啡依赖大鼠脑内相关核团多巴胺D1、D2受体基因表达的影响

目的 研究吗啡依赖对大鼠中脑边缘多巴胺(DA)系统内相关核团DA受体的影响及四氢原小檗碱(THPB)对其的效应。方法 将30只SD大鼠随机分为5组,每组6只。正常对照组始终给予等量生理盐水腹腔注射,4组建立吗啡依赖模型。以5 mg/kg开始腹腔注射,2次/d,每次递增5 mg,一直增至第10天每次50 mg/kg;第11天起对其中的两组分别注射生理盐水12 d(Mor NS12组)和30 d(Mor NS30组),另两组分别注射30 mg/kg THPB 12 d(Mor THPB 12组)和30 d(Mor THPB 30组)。分别测定中脑腹侧被盖区(VTA)等脑结构酪氨酸单氧化酶(TM)免疫阳性神经元的平均吸光度(A)值、D1R mRNA和D2R mRNA水平。结果 与正常对照组相比,Mor NS组大鼠VTA的TM表达持续增高(P<0.01)。治疗12 d时,Mor NS12组D1R mRNA在伏隔核、杏仁核、尾壳核、前额叶皮质的含量和D3R mRNA在VTA、尾壳核、伏隔核的含量均低于正常对照组(P<0.01),而Mor THPB12组在伏隔核、杏仁核、尾壳核的D1R mRNA含量和VTA、尾壳核的D2R mRNA的含量与正常对照组的差异无显著性。治疗30 d时,Mor NS30组D1R mRNA(除杏仁核外)和D2R mRNA在各脑区的含量仍低于正常对照组(P<0.01);而Mor THPB30组D1R mRNA除前额叶皮质外的含量和D2R mRNA的含量已至正常水平。结论 THPB能抑制阿片依赖状态下VTA的TM免疫     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

Inhomogeneities in the propagation of the slow wave in the stomach

The propagation of the slow wave in the stomach and its role in inducing sweeping peristaltic contractions toward the pylorus, essential for a proper digestion and emptying, have been studied for many years. Irregularities in the timing or in the pattern of propagation of the slow wave have been known to induce various gastric malfunctions and, recently, several types of gastric dysrhythmias have been described which could lead to gastric contraction abnormalities. In this study, Du et al. have analyzed the disturbances caused by a simple transmural incision in a human stomach, performed to obtain a biopsy of the muscle, on the propagation pattern of the slow wave. In addition, they show that such an incision may by itself also induce new types of gastric dysrhythmias. These results are important in demonstrating that the function of the stomach can easily be disturbed by such procedures. This mini‐review describes several ways in which inhomogeneities in propagation may affect the conduction pattern of the slow wave, including the genesis of several dysrhythmias, and what is currently known about their impact on gastric contraction and digestion.     

Dysthymic disorder in the aged in the community

Summary The prevalence of dysthymic disorder and and its relationship to social and health variables were investigated in a Finnish population aged 60 years or over. The prevalence was lower in men (17.2 per 100) than in women (22.9 per 100). In the total population the occurrence was higher in the widowed (24.9 per 100) than in the married (18.3 per 100). In men, dysthymic disorder was more common in those with a lower educational level (22.6 per 100) than with a higher educational level (15.1 per 100), and more common in persons receiving long-term institutional care or home nursing or home help (28.7 per 100) than in persons living independently at home (14.6 per 100). The rate was not related to age, marital status or occupation. In women, the occurrence was not related to age, marital status, education, occupation or form of social and health care. The female rate was higher than the male in the older group (70 yrs. +), in married persons, in those with a higher educational level and in those living independently at home. Underdiagnosing was evident. The occurrence of dysthymic disorder was related to poor health and poor functional status and to the occurrence of social and health stressors. No differences were found in the occurrence of the related factors between persons with dysthymic disorder and persons with major depression. Our results support the conclusion that the majority of cases of dysthymic disorders in the elderly are affective illnesses and not personality disorders.     

Early stages in the formation of the cerebellum in the frog

The formation of the cerebellum was studied during the first 6 months of the tadpole stage of the bullfrog by using standard histological methods and reconstructions from serial horizontal sections. Three major developmental phases were noted in the formation of the cerebellum. (1) During the first 5 weeks of development, the neuroepithelium proliferated and the dorsal mesencephalic plates increased in size. (2) Starting in the sixth week, a patch of neuroepithelium began to differentiate and gave rise to a small population of Purkinje cells. In subsequent weeks, the area of differentiation continued to spread and a Purkinje cell layer became established along the dorsal margin of the cerebellar plate. (3) In the 12th week, the ventrolateral part of the cerebellar plate began to increase in size and generate two populations of small cells. The lateralmost part of the neuroepithelium in this area generated a group of cells that formed an external granular layer that was one cell deep. Cells of this external granular layer migrated inward into the primitive molecular layer, and by the 26th week only a remnant of an external granular layer remained in the cerebellum. The more medially situated part of the neuroepithelium gave rise to another population of small cells that formed a column, which appeared to be continuous with the Purkinje cells, but differed from them in size. It should be noted that full maturation of the cerebellum occurs during metamorphosis, which in this species remains some 2 years away.     

Cells in the pretectal olivary nucleus are in the pathway for the direct light reflex of the pupil in the rat

Extracellular microelectrode recordings from 148 single cells in the pretectum of the hooded rat were classified according to their temporal response properties to light stimulation of their retinal receptive fields. Fifty-six cells were classified as tonic-on cells, 22 cells were classified as tonic-off cells, and 53 cells were classified as phasic cells. Seventeen cells could not be assigned to one of these 3 groups. The diameters of the receptive field centers of the tonic-on pretectal cell were clustered about a mean of 31° and the temporal response of these cells was sustained. Constriction of the contralateral pupil was produced by electrical stimulation through the recording electrode at sites containing tonic-on pretectal cells, but not at sites containing tonic-off pretectal cells or phasic pretectal cells. For this reason, we argue that tonic-on cells are likely to mediate constriction in the light reflex of the rat's pupil. Receptive field maps together with electrolytic marking lesions at recording and stimulation sites showed that tonic-on pretectal cells are retinotopically organized and are aggregated in a strip running from the dorso-medial tip of the pretectum to the ventro-lateral boundary. The anatomical distribution of these cells is coextensive with the region known as the pretectal olivary nucleus (PO) in the rat^26,27.Using fine microelectrodes, recordings were obtained from 27 axons presumed origin (fibers). Of these, 14 were tonic-on, 10 were phasic, 2 were tonic-off, and 2 were unclassified. Recordings from tonic-on fibers were obtained near tonic-on pretectal cells, typically in the most dorsal light-responsiveness region of the pretectum. These fibers were activated by single pulse electrical stimulation of the optic chiasm. The mean receptive field center diameter of 6 tonic-on fibers was 10.1°, or about a factor of 3 less than that of pretectal tonic-on cells. The mean conduction velocity of 14 tonic-on fibers was 3.1 m/s.We argue that the tonic-on cells of the PO serve to integrate signals from tonic-on center retinal ganglion cells with adjacent receptive fields to provide signals for constriction of the pupil to neurons in the oculomotor nucleus.     

Organization in the descending tracts of the dorsolateral funiculus in the cat

Organization of the fibers in the descending tracts of the dorsolateral funiculus of the cervical spinal cord was investigated in cats. The spinal cord was penetrated with microelectrodes at 400 mum intervals in the medio-lateral direction at the c5/c6 and c6/c7 segmental borders. Silicon substrate microelectrodes with a linear arrangement of activated iridium contacts were used. The stimulus consisted of a 20 ms train of charge balanced biphasic current pulses at 330 Hz. The evoked activities from selected forelimb muscles were acquired into computer. Only the data points with an activation threshold of less than 35 muA were considered in the analysis. Muscle contractions were mostly in the form of short twitches. In both spinal segments, an area of high threshold was found in the middle of the dorsolateral funiculus. Majority of the muscles studied had a dorsal or ventral concentration of activation points. The distal muscles were mostly activated in the ventro-lateral aspect of the funiculus, while the elbow muscle maps spread to both dorsal and ventral sides. These results show a functional organization in both cervical segments studied, with overlapping regions between the areas dedicated for each forelimb muscle.     

Asymmetry in the structural organization of the ganglion layer of the retina in the frog

Silver-impregnated retinal preparations were used to study the distribution density and topographic features of small and large ganglionic cells (GC) of Rana ridibunda and Rana temporaria. For both species the increased density of GC (a streak) stretched higher than the naso-temporal axis passing through the optic disk. Beyond the streak the density of small GC was maximal in the central zone of the retina and decreased towards its periphery. For the upper quadrants of the retina the density of small GC was higher than that for the lower ones by 26% on the average. On the contrary, the density of large GC was higher in the lower part of the retina as compared to the upper one, the difference being more pronounced for R. temporaria. The density of large GC was also asymmetric with respect to the dorso-ventral axis being higher in nasal quadrants than in temporal ones by 40-55%. The highest density of large GC was found in the middle zone of the retina. The found structural asymmetry in the retinal output raster may bear an adaptively ecological meaning and may condition the particularities of the formation of the visually guided prey-catching and avoidance reactions.     

Experiences in the United States--a difference in the status in the United States and that in Japan]

Child and adolescent psychiatry has been established as a subspecialty in the United States. The systematic education, training and research opportunities are currently available and child and adolescent psychiatry is a major part of psychiatric practice in the US. However, there are many burdens to overcome to provide adequate child mental health care. Several important focus on child mental health care in US are to 1) improve the assessment of and recognition of mental health needs in children, 2) promote scientifically-proven and evidence based interventions and 3) increase access to and coordination of quality mental health care services. To understand the current status and problems in child and adolescent psychiatry in US may help the Japanese psychiatrists to develop and establish child and adolescent psychiatry in Japan.     

Apoplexy in the everyday practice in the eighteenth century

We report the original recipes applied to treat apoplexy in the eighteenth century, as written in the personal notes of doctor of that century.