The effect of restraint stress on the discriminative stimulus properties of heroin and the role of the opioid receptor activation in the ventral tegmental area in heroin discrimination were examined. In Experiment 1, male rats were trained to discriminate heroin (0.5 mg/kg, SC) from saline under conditions of exposure to restraint (15 min/day; three times a week) or no stress. Dose-response curves were subsequently determined under conditions of no stress, restraint, corticosterone (3 mg/kg, IP), and saline. Exposure to restraint during training did not alter heroin discrimination under any of the conditions tested. In contrast, administration of restraint or the stress hormone corticosterone just prior to drug injections decreased sensitivity to the heroin cue. In Experiment 2, injections of morphine (5-10 micrograms/side) into the ventral tegmental area (VTA, the cell body region of the mesocorticolimbic dopamine neurons) did not result in heroin-appropriate responding in animals trained to discriminate heroin injected systemically from saline. Furthermore, intra-VTA injections of the opioid antagonist methyl naltrexone (0.75-3.0 micrograms/side) did not block the discriminability of heroin given systemically. These results indicate that exposure to restraint stress or the stress hormone corticosterone in close temporal contiguity to the drug injection may reduce the sensitivity to the opioid cue. In addition, under the condition of the present experiment activation of opioid receptors in the VTA does not appear to mimic the discriminative stimulus effects of systemically administered heroin.

Animals↗

PubMedDate not supplied

Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity.

Progress has been made over the last 10 years in determining the neural mechanisms of sensitization induced by amphetamine-like psychostimulants, opioids and stressors. Changes in dopamine transmission in axon terminal fields such as the nucleus accumbens appear to underlie the expression of sensitization, but the actions of drugs and stressors in the somatodendritic regions of the A10/A9 dopamine neurons seem critical for the initiation of sensitization. Manipulations that increase somatodendritic dopamine release and permit the stimulation of D1 dopamine receptors in this region induce changes in the dopamine system that lead to the development of long-term sensitization. However, it is not known exactly how the changes in the A10/A9 region are encoded to permit augmented dopamine transmission in the terminal field. One possibility is that the dopamine neurons of sensitized animals have become increasingly sensitive to excitatory pharmacological and environmental stimuli or desensitized to inhibitory regulation. Alternatively, changes in cellular activity or protein synthesis may result in a change in the presynaptic regulation of axon terminal dopamine release.

Animals↗

PubMedDate not supplied

The effects of life-long food restriction on spatial memory in young and aged Fischer 344 rats measured in the eight-arm radial and the Morris water mazes.

The effect of life-long 60% ad lib food restriction on performance in two tasks involving spatial memory, the eight-arm radial maze and the Morris water maze, was studied in young and aged Fischer 344 rats. Restricted (R) and ad lib (AL) feeding groups were compared at 8, 16, and 24 months of age on both tasks. A 30-month-old R group was also tested in the Morris water maze. In the eight-arm maze, although 24-month-old animals performed more poorly than 8- and 16-month-old animals during the first week of testing, overall accuracy of performance did not vary significantly as a function of age. Twenty-four-month-old animals took longer to make 10 choices than did younger animals, and there was a significant interaction between feeding regimen and age, reflecting the fact that at the two younger ages, R groups performed more quickly than the AL groups. In the Morris water maze, both distance swum and time to find the platform increased with age. Life-long food restriction led to small but significant improvements in performance in the water maze in aged rats. R groups showed evidence for better retention over 24-hour intervals than did AL groups. By 30 months of age, however, R animals showed impaired performance relative to younger R groups. These differential findings on the two tasks, as they were used here, suggest that there was greater impairment with age on the spatial memory task requiring retention of information over long intervals than there was on the task primarily involving working memory within a trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMedDate not supplied

Effect of tumor necrosis factor alpha and beta on human oligodendrocytes and neurons in culture.

Cytokines produced by infiltrating hematogenous cells or by glial cells activated during the course of central nervous system disease or trauma are implicated as mediators of tissue injury. In this study, we have assessed the extent and mechanism of injury of human-derived CNS oligodendrocytes and neurons in vitro mediated by the cytokines tumor necrosis factor alpha and beta and compared these with the tumor necrosis factor independent effects mediated by activated CD4+ T-cells. We found that activated CD4+ T-cells, but not tumor necrosis factor alpha or beta, could induce significant release of lactate dehydrogenase, a measure of cell membrane lysis, from oligodendrocytes within 24 hr. Neither induced DNA fragmentation as measured using a fluorescence nick-end labelling technique. After a more prolonged time period (96 hr), tumor necrosis factor alpha did induce nuclear fragmentation changes in a significant proportion of oligodendrocytes without increased lactate dehydrogenase release. The extent of DNA fragmentation was comparable to that induced by serum deprivation. Tumor necrosis factor beta effects were even more pronounced. In contrast to oligodendrocytes, the extent of DNA fragmentation, assessed by propidium iodide staining, induced in neurons by tumor necrosis factor alpha was less than that induced by serum deprivation. In-situ hybridization studies of human adult glial cells in culture indicated that astrocytes, as well as microglia, can express tumor necrosis factor alpha mRNA.

Adult↗

PubMedDate not supplied

Profile: the home for all children.

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Adoption↗

PubMedDate not supplied

Multi-drug resistance genes in the management of neoplastic disease.

P-gp can function as an ATP-dependent cytotoxic drug-efflux pump. In normal tissues, protein expression is localized to cell surfaces that face excretory lumina; hence, P-gp may function as a toxic-waste disposal system. Tumors that are derived from these tissues can be high expressors of P-gp, and these tumors tend to display intrinsic chemoresistance. Other non-expressing tumors can become P-gp positive after treatment or at relapse, suggesting that mdr may be involved in acquired resistance. The use of MDR-modifying agents has had some clinical success, and further trials of chemosensitizers are proceeding. P-gp overexpression does not explain how clinical resistance to anthracyclines, alkylating agents, and cis-platinum can arise simultaneously. In these cases, multiple genetic mechanisms of resistance may coexist. Eventually, mdr status can be used to select the most effective chemotherapy protocol for the individual. Currently, conversion of a previously mdr negative tumor to mdr expression, in the face of clinical resistance, justifies changing to a non-MDR drug protocol, or if not feasible, the use of MDR sensitizers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Risk management in a psychiatric hospital: Wichita Falls State Hospital.

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Hospital Bed Capacity, 500 and over↗

PubMedDate not supplied

Natural history of otitis media in the American native.

Otitis media is the leading reportable disease among the Indian and Eskimo population. In addition, its prevalence is more frequent in American natives than in Caucasians or Negroes. An attempt herewith is made to delineate the factors that account for the high prevalence of otitis media in the acute and chronic form. Secondly, the characteristic morbid complications of otitis media in this population are evaluated.

Adolescent↗

PubMedDate not supplied

Alzheimer's disease. 1: Pathology, aetiology and treatment.

Alzheimer's disease is a progressive disorder which accounts for a large proportion of people diagnosed with dementia. This article, the first in a two-part series, discusses the pathology, aetiology and possible treatment of the condition.

Alzheimer Disease↗

PubMedDate not supplied

Aphasia: a care study.

Aphasia is a term used to describe any deficit in the production or comprehension of speech. Damage to various parts of the brain can give rise to aphasia. The communication problems experienced by patients with aphasia present a unique challenge to the nurse. It is vital that all patients receive a proper assessment of their needs. A holistic approach is required. Nurses should be non-judgmental in their approach and remember the person behind the aphasia.

Aged↗

PubMedDate not supplied

The relationship of physical activity and cardiovascular fitness to absenteeism and medical care claims among law enforcement officers.

BACKGROUND: Previous research has shown an inverse relationship between cardiovascular fitness and both absenteeism and health care costs. The documentation of these relationships with law enforcement officers will support the usefulness of providing health promotion programs for this population. METHODS: Data were collected over a one-year period to examine the relationship of physical activity and cardiovascular fitness to absenteeism and medical care claims among law enforcement officers (N = 734). RESULTS: Analysis of covariance indicated that sedentary officers were absent significantly more often than active officers; also, female officers were absent significantly more than male officers. Although proportionally more female officers than males scored above the 50th percentile on fitness (based on Cooper's norms), increased fitness for females was not related to decreased absenteeism. Increased fitness for male officers was related to decreased absenteeism. Medical care claims for a sub-sample of male officers (N = 363) were lower for more fit and more active officers, although this relationship was nonsignificant. DISCUSSION: These observational data strengthen the hypothesis that absenteeism levels of physically active officers are lower than those of sedentary officers. For females, the relationship of absenteeism to family issues associated with child care and pregnancy leave in the workplace appears worthy of examination.

Absenteeism↗