Compartmental changes in expression of c-Fos and FosB proteins in intact and dopamine-depleted striatum after chronic apomorphine treatment

Chronic administration of dopaminergic agonists to rats with unilateral 6-OH-dopamine (6-OHDA) lesions of nigrostriatal pathway produces behavioral sensitization to subsequent agonist challenges and may serve as a model for DOPA-induced dyskinesias. In order to understand striatal mechanisms behind this long-term behavioral change we examined striatal c-Fos and FosB immunoreactivity induced by apomorphine challenge (5 mg/kg, s.c.) after 3 days of withdrawal following a 2-week administration (5 mg/kg, b.i.d., s.c.) both in intact and 6-OHDA-lesioned animals. In intact rats, c-Fos induction by acute apomorphine exposure showed a striosomal pattern, whereas FosB immunopositivity was diffusely distributed. Following chronic administration, FosB induction turned to a clear striosome dominant pattern similar to c-Fos expression. In denervated striatum, expression of both proteins was profoundly augmented in a homogeneous pattern after a single dose of apomorphine. A distinct striosomal patterning appeared after chronic apomorphine administration in ventromedial part of the denervated striatum with a down-regulation in the matrix and relative enhancement in striosomes. These results suggest that compartmental reorganization of striatal neuronal activity may play a role in long-term behavioral changes induced by chronic dopaminergic treatments both under normal and dopamine-depleted conditions.     

Ginkgo biloba extract EGb761 reduces the development of amphetamine-induced behavioral sensitization: effects on hippocampal type II corticosteroid receptors

Pretreatment of rats with the extract of Ginkgo biloba termed EGb761 reduced the behavioral sensitization induced by successive -amphetamine administrations (0.5 mg/kg) as estimated by increasing values of locomotor activity. EGb761 pretreatment also prevented the reduced density of [³H]dexamethasone binding sites in the dentate gyrus and the CA1 hippocampal regions of -amphetamine treated animals. These observations suggest that EGb761, by reducing glucocorticoid levels, could modulate the activity of the neuronal systems involved in the expression of the behavioral sensitization.     

The involvement of an opiate mechanism in the sensitized behavioral deficit induced by early chronic variable stress: influence of desipramine

The influence of early chronic variable stress (CVS) associated with persistent desipramine (DMI) administration was examined on escape performance. Animals were exposed to CVS and 1 day later administered DMI (5 mg/kg, i.p. twice a day) or vehicle (VH) during six consecutive days. Escape performance was assessed over 24 h following inescapable shock (IS) exposure. Higher escape failures were observed in CVS shocked rats compared with unstressed shocked animals. DMI normalized escape failures in both groups. In order to investigate the role of an endogenous opiate mechanism presumably activated by CVS exposure in this behavioral deficit, rats were administered naltrexone (NAL, 2 mg/kg i.p.) or VH prior to each daily stressor of the CVS regime. NAL pretreatment blocked escape failures performed only by CVS shocked rats. In addition, animals were daily administered morphine (MOR, 10 mg/kg, i.p.) or VH during seven consecutive days and subsequently administered DMI. A significant increase in escape deficit in shocked rats was observed after chronic MOR but not following the associated treatment with MOR and DMI. These behavioral data suggest that early experience with a CVS facilitated the onset of escape deficit induced by a brief IS event, an effect that can be prevented by chronic DMI. Furthermore, this sensitized escape deficit response seems to be partially modulated by the previous activation of an opiate mechanism.     

Acute and chronic effects of nornicotine on locomotor activity in rats: altered response to nicotine

Rationale: Nicotine, a tobacco alkaloid, is known to be important in the acquisition and maintenance of tobacco smoking. Nornicotine, an active nicotine metabolite, stimulates nicotinic receptors and may produce psychomotor effects similar to nicotine. Objective: The present study determined the effects of acute and repeated administration of nornicotine on locomotor activity and compared its effects with those of nicotine. Methods: R(+)-Nornicotine (0.3–10 mg/kg), S(–)-nornicotine (0.3–10 mg/kg), S(–)-nicotine (0.1–1 mg/kg) or saline was administered s.c. to rats acutely or repeatedly (eight injections at 48-h intervals). Activity was recorded for 50 min immediately after each injection. Results: S(–)-Nicotine produced transient hypoactivity, followed by dose-related hyperactivity. Repeated S(–)-nicotine administration resulted in tolerance to the hypoactivity and sensitization to the hyperactivity. Subsequent testing following a saline injection revealed evidence of conditioned hyperactivity. Acute administration of 0.3 mg/kg or 1 mg/kg R(+)- or S(–)-nornicotine produced no effect. Transient hypoactivity was observed at 3 mg/kg and 10 mg/kg R(+)-nornicotine and at 10 mg/kg S(–)-nornicotine. However, rebound hyperactivity was not observed following acute administration of either nornicotine enantiomer, suggesting that nornicotine-induced psychomotor effects differ qualitatively from those of S(–)-nicotine. Repeated R(+)-nornicotine resulted in tolerance to the transient hypoactivity, however hyperactivity was not observed. Repeated S(–)-nornicotine resulted in tolerance to the hypoactivity and the appearance of hyperactivity. Repeated administration of either nornicotine enantiomer resulted in a dose-dependent alteration in response to a 1 mg/kg S(–)-nicotine challenge, suggesting some commonalities in the mechanism of action. Conclusion: Nornicotine likely contributes to the neuropharmacological effects of nicotine and tobacco use. Received: 11 January 1999 / Final version: 25 March 1999     

Effects of drug history on the acquisition of responding maintained by GBR 12909 in rhesus monkeys

The reinforcing effects of cocaine have been associated with its actions at the dopamine reuptake site. Previous studies have shown that selective dopamine reuptake inhibitors can attenuate cocaine self-administration in animals, suggesting that they may serve as pharmacotherapeutic agents. In order to assess the potential reinforcing effects of one of these agents, the acquisition and maintenance of GBR 12909 self-administration were studied in different groups of rhesus monkeys (Macaca mulatta) that were either experimentally naive or experienced with respect to the self-administration of cocaine or GBR 12909. Lever-pressing was maintained under a multiple FR30 schedule with alternating components of either food or drug presentation. Experimentally naive monkeys failed to self-administer low doses of GBR 12909 (3–30 µg/kg per injection). However, after a history of cocaine self-administration, GBR 12909 (56 µg/kg per injection and then 30 µg/kg per injection) maintained numbers of drug deliveries similar to those maintained by cocaine. When another group of experimentally-naive monkeys was initially exposed to GBR 12909 self-administration, 56 µg/kg per injection failed to maintain responding. However, subsequent exposure to 100 µg/kg per injection established GBR 12909 self-administration, and high levels of responding were sustained later when the unit dose was decreased to 30 µg/kg per injection. In monkeys with prior experience with cocaine self-administration (75 sessions) unit doses of either 30 µg/kg per injection or 56 µg/kg per injection GBR 12909 maintained responding. In another group of monkeys with a more extensive history of cocaine self-administration (320 sessions), unit doses of either 10 µg/kg per injection or 30 µg/kg per injection GBR 12909 maintained responding. These results show that drug-maintained responding can be established with higher unit doses of GBR 12909. After exposure to these higher, more effective doses of GBR 12909, or effective doses of cocaine, lower doses of GBR 12909 are more likely to support drug-maintained responding.     

特区经济学的理论前提

实行特殊政策和实施特殊管理体制是世界经济特区共有的基本特征。正是这两个基本特征构成了特区经济学的两个理论前提。对经济特区实行特殊政策和实施特殊管理体制进行理论分析 ,目的在于为构筑特区经济学的理论体系作理论上的准备     

儿童期单纯肥胖症的行为治疗

为研究适合中国肥胖儿童的行为治疗方案及效果，对２４例（男女各１２例）１３岁单纯肥胖儿童进行３年行为治疗纵向研究。２４名同年龄、性别、年级非肥胖儿童为正常对照组。观测参数有身高、体重、四处皮脂、腰、臀围及其比例、有氧运动能力（最大耐受时间和运动距离）。体育测试成绩包括引体向上、跳远、８００米跑、仰卧起坐，满分为３０分。按运动处方每天运动２小时，每周５天。在医生指导下肥胖儿童写行为分析和行为矫正方案。有关肥胖指标年减少率（男／女）体脂含量为２３％～４２％，肥胖度２．８％～２．１％，腰／臀比２．５％～２．６％，四处皮脂和５．７％女０．８％～１．０％），有氧能力明显进步。体育成绩肥胖干预组３０％达满分，７０％为２７～２９分。肥胖对照组６０％为２０分，３０％为１５～１９分。提示儿童期单纯肥胖症的干预方案应以健康教育和运动处方为基础，行为治疗为核心技术；在家庭日常生活中持续进行，家长、教师、医务人员应共同参与。     

The dopamine D3 receptor antagonist nafadotride inhibits development of locomotor sensitization to amphetamine

Behavioral sensitization is a well-studied model of behavioral plasticity mediated at least in part by dopaminergic systems believed to play an important role in several psychiatric conditions. In the rodent, locomotion is regulated by the opposing balance of D3 and D2 receptors, with D2 activation increasing and D3 stimulation inhibiting locomotion. However, receptor occupancy of D3 dopamine receptors is far greater than D2 or D1 occupancy at typical post-stimulant dopamine concentrations. We therefore hypothesized that tolerance of D3 receptor inhibition of locomotion contributes to the development of sensitization. To test this hypothesis, we examined the effect of the D3 receptor antagonist nafadotride on sensitization. As predicted, nafadotride inhibits augmentation of the locomotion response to repetitive amphetamine. This finding is consistent with the proposed model of adaptive down-regulation of D3 dopamine receptor function contributing to the development of behavioral sensitization.     

沈阳市行为问题儿童的个性特征分析

目的了解儿童行为问题的发生情况及行为问题儿童的个性特征,以便开展对行为问题儿童采取干预措施提供依据.方法采用Rutter儿童行为问卷父母用表对沈阳市2所小学一～六年级每个年级2个班学生进行行为测试,采用EPQ个性问卷手册(儿童用)对三～六年级学生进行个性测试,并进行统计分析.结果行为问题检出率为10.75%.经t检验,行为问题与神经质和掩饰性2个因素有关;经Logistic分析,儿童个性不稳定倾向为行为问题发生的相关因素.结论儿童行为问题的发生与个性特征有一定的关系.行为问题儿童个性趋向于神经质且掩饰性低;儿童行为问题的发生与性别有关,男孩检出率明显高于女孩.有必要培养儿童逐渐形成健全的个性,并进行心理健康指导.     

700名医学生心理卫生状况的调查分析

目的了解郴州市大学生心理卫生状况.方法采用症状自评量表(SCL-90)对郴州市某医学高等专科学校700名大学生进行问卷调查.结果被试中至少有一个SCL-90因子的得分大于或等于3分的学生占11.57%,男、女及不同来源的学生间比较,均无统计学意义:但三年级学生比例高于一、二年级学生以及学护理专业学生高于临床医学专业学生,且具有统计学意义;总体上,郴州市大学生心理卫生水平差于全国常模,但优于国内其他地区大学生;女生、三年级学生及护理学专业学生的心理问题相对较为突出.结论大学生的心理问题不容忽视,应针对不同群体采取不同措施,加强大学生心理健康教育.