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Parkinson JA Dalley JW Cardinal RN Bamford A Fehnert B Lachenal G Rudarakanchana N Halkerston KM Robbins TW Everitt BJ 《Behavioural brain research》2002,137(1-2):149-163
The involvement of mesoaccumbens dopamine in adaptive learning and behaviour is unclear. For example, dopamine may act as a teaching signal to enable learning, or more generally modulate the behavioural expression, or selection, of an already-learned response. The present study investigated the involvement of the mesoaccumbens dopamine system in a fundamental form of learning: Pavlovian conditioning. In this case, the temporal association of a previously neutral visual stimulus and a biologically significant unconditioned stimulus (US), subsequently led to the production of the conditioned response (CR) of discriminated approach behaviour directed toward the conditioned stimulus (CS+), relative to a control (CS-) stimulus. 6-hydroxydopamine lesions of the nucleus accumbens (NAcc), leading to approximately 80% reductions in tissue dopamine, were made at varying time points in four experimental groups of rats, either before or subsequent to the acquisition of the CR. NAcc dopamine depletion produced long-term neuroadaptations in dopamine function 2 months after surgery, and profoundly impaired discriminated Pavlovian approach regardless of when the lesion was made. Thus, NAcc dopamine not only plays a role in conditioned behavioural activation, but also in making the appropriate discriminated response i.e. the direction of response. Further, acquisition lesions produced a far greater impact on discriminated approach than performance lesions. This difference in lesion-induced impairment implies that mesoaccumbens dopamine may play differential roles in the learning and performance of preparatory Pavlovian conditioning. 相似文献
94.
The addition of positron emission tomography (PET) information to CT‐based radiotherapy treatment planning has the potential to improve target volume definition through more accurate localization of the primary tumour and involved regional lymph nodes. This case report describes the first patient enrolled to a prospective study evaluating the effects of coregistered positron emission tomography/CT images on radiotherapy treatment planning for oesophageal cancer. The results show that if combined positron emission tomography/CT is used for radiotherapy treatment planning, there may be alterations to the delineation of tumour volumes when compared to CT alone. For this patient, a geographic miss of tumour would have occurred if CT data alone were used for radiotherapy planning. 相似文献
95.
Preclinical evidence for therapeutic efficacy of selective estrogen receptor modulators for uterine leiomyoma 总被引:7,自引:0,他引:7
Walker CL Burroughs KD Davis B Sowell K Everitt JI Fuchs-Young R 《Journal of the Society for Gynecologic Investigation》2000,7(4):249-256
OBJECTIVE: Uterine leiomyoma are the most common gynecologic neoplasm and a primary cause of hysterectomy in premenopausal women. Preclinical studies were conducted in the Eker rat model to investigate the potential efficacy of selective estrogen receptor modulators (SERMs) as therapeutic agents for this tumor. METHODS: Twelve-month-old Eker rats were randomized into five treatment arms including tamoxifen, placebo, LY 326315, vehicle, and no treatment. Additional animals received ovariectomy or sham surgery at 4 months of age to determine the effect of ovarian ablation on tumor development. The study was terminated after 2 to 4 months of treatment, and tumor incidence, size, proliferative and apoptotic indices were determined. Size and incidence data were subjected to chi-square analysis. One-way analysis of variance and Fisher's least significant difference tests were used to compare proliferative and apoptotic indices. RESULTS: Ovariectomy virtually ablated leiomyoma development, indicating that these tumors were dependent on ovarian hormones for growth and development. Treatment with tamoxifen or raloxifene analog LY 326315 reduced leiomyoma incidence by 40-60% and reduced the size of remaining tumors. The effect of SERMs on leiomyomas was mediated by a decrease in cell proliferation without a decrease in apoptotic index. CONCLUSION: SERMs have been shown to be therapeutically efficacious against breast cancer and to reduce tumor incidence in women at increased risk for this disease. The present data indicate that therapeutic efficacy may also be extended to uterine leiomyoma and demonstrate the utility of this animal model for preclinical studies to identify new therapeutic modalities. 相似文献
96.
To investigate further the cholinergic specificity of the effects of basal forebrain lesion-induced disruption of attentional performance, the present study examined the efficacy of various pharmacological agents in improving performance of a five-choice serial reaction time task in rats that had received lesions of the cholinergic basal forebrain. Specifically, the effects of the novel 5-HT3 receptor antagonist, ondansetron (0.3, 1, 10 ng/kg), and of nicotine (0.03, 0.06, 0.1, 0.3 mg/kg) and the anticholinesterase, physostigmine (0.05, 0.1 mg/kg), on attentional function were examined in animals which had received AMPA-induced lesions of the nucleus basalis magnocellularis (nbM). The behavioural impairments observed immediately following the lesion were a reduction were choice accuracy and an increase in correct response latency. Although these impairments showed recovery over the course of the following weeks, the deficit in choice accuracy could be reinstated by reducing the duration of the visual stimulus and thus increasing the attentional load placed on the animals. This reduction in choice accuracy could be dose dependently improved by systemic administration of either physostigmine or nicotine, suggesting that this impairment in attentional function may be attributed to disruption of cholinergic function. The pharmacological specificity of these improvements was supported by the inability ofd-amphetamine to improve task performance (0.2, 0.4, 0.8 mg/kg). Ondansetron was also unable to improve accuracy of performance in lesioned animals, but was effective in reducing the anticipatory or premature responding observed in both control and lesioned animals, even when elevated (in the case of controls) by treatment with systemicd-amphetamine. The results of the present study therefore suggest that cholinergic dysfunction can lead to attentional impairments which can be ameliorated by cholinergic treatments such as physostigmine and nicotine, but that ondansetron, despite its proposed ability to release cortical acetylcholine, was unable to restore choice accuracy at the doses employed. The results further suggest a double dissociation of effects on accuracy and the disinhibition of responding. 相似文献
97.
David Eilam Hazel Talangbayan Gitanjali Canaran Henry Szechtman 《Psychopharmacology》1992,106(4):447-454
The study compares the behavioral profiles induced in rats (N=118) by the D2-dopaminergic receptor agonist quinpirole (0.03 and 0.5 mg/kg), and the D1-agonist SKF38393 (1.25–40 mg/kg), and both agonists administered together. Locomotion and snout contact frequency were reduced by the low but increased by the high dose of quinpirole; SKF38393 also reduced these behaviors and attenuated the effect of the high quinpirole dose. Only the high dose of quinpirole increased the duration of snout contact bouts and the frequency of mouthing; SKF38393 had no effect but in combination with the high dose of quinpirole, it enhanced the performance of these behaviors greatly. The duration of mouthing bouts was not affected by either agonist but was greatly extended when SKF38393 was administered together with the high dose of quinpirole. Grooming was inhibited by both the low and the high dose of quinpirole, and stimulated by the injection of SKF38393 or its addition to the low dose of quinpirole. These findings suggest that snout contact is controlled by modulating the frequency of episodes whereas mouthing is controlled by modulating the duration of episodes. Moreover, although they do not disprove the prevailing notion of D1–D2 receptor synergism, the present data are consistent also with an oppositional model of D1–D2 receptor interaction in the regulation of locomotion, snout contact, mouthing, and grooming in intact animals. 相似文献
98.
Clifford Katy; Rai Raj; Watson Hazel; Regan Lesley 《Human reproduction (Oxford, England)》1994,9(7):1328-1332
A total of 500 consecutive women (mean age 32.9 years; SD 5years) presenting with a history of recurrent miscarriages (median4; range 317) were investigated for the presence of antiphospholipidantibodies (APA), polycystic ovaries (PCO), hypersecretion ofluteinizing hormone (LH) and chromosome abnormalities in orderto detect an underlying cause of their pregnancy losses. Allwomen had details of their previous reproductive history, investigationsand treatment documented: 76% of the women had experienced onlyearly pregnancy losses (miscarriage <13 weeks gestation);32% had a history of subfertility; and significant parentalchromosome rearrangements were present in 3.6% of couples. Anultrasound diagnosis of PCO was made in 56% of women, 58% ofwhom were demonstrated to hypersecrete LH, based on early morningurinary LH analysis. Circulating APA were found in 14% of women.An underlying cause of recurrent miscarriagegenetic,endocrine or autoimmunewas found in >50% of couples.Women in the latter two groups are being recruited to randomizedtreatment trials which are discussed. 相似文献
99.
用血清学方法对胃癌高发区兰州地区3781名各年龄组健康人群进行前瞻性幽门螺杆菌(Helicobacterpylori,HP)感染调查,并与胃癌低发区广州地区的资料进行比较。结果显示:兰州地区HP总感染标化率为61.6%,高于广州地区的48.3%(P<0.001)。两者之间的差异在10岁以下儿童,尤其是4岁以下幼儿最显著(分别为43.2%与19.3%,P<0.001);兰州地区HP阳性率的高峰年龄段在30~39岁,比广州地区提早10年以上出现,可能与胃癌高发区人群较早出现HP相关性萎缩性胃炎及肠上皮化生有关。 相似文献
100.