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OBJECTIVE To identify single-nucleotide polymorphisms (SNPs) associated with risk and age at onset of Alzheimer disease (AD) in a genomewide association study of 469 438 SNPs. DESIGN Case-control study with replication. SETTING Memory referral clinics in Canada and the United Kingdom. PARTICIPANTS The hypothesis-generating data set consisted of 753(More)
Animals exposed to cold-water swims, rotation, or inexcapable shocks, display analgesia comparable to that of 10 mg/kg of morphine. The present study investigated whether a narcotic antagonist would eliminate analgesia induced by cold-water swims. In one group of 12 rats, naloxone at 0, 1, 5, 10 and 20 mg/kg was administered at weekly intervals immediately(More)
Extensive evidence has indicated that distinct neural systems specifically designed to inhibit sensitivity to painful stimuli exist. Recent advances suggest that the endorphins, enkephalins and the opiate receptor interact with a descending serotonergic bulbospinal system to mediate the analgesic responses to opiates and electrical stimulation. In assessing(More)
In three experiments, the locus of tail stimulation in the tailflick assay was found to be an important parameter in determining morphine action. Rats were intravenously infused (Experiment I), injected with morphine subcutaneously (Experiment II), or implanted subcutaneously with morphine pellets (Experiment III). Analgesia was evaluated periodically(More)
Animals exposed to cold-water swims, rotation, inescapable shocks, abrupt food deprivation and other stressors display temporary analgesia. Since repeated exposures result in adaptation of this analgesia in much the same way that repeated administration of opiates results in tolerance, the possibility of cross-tolerance between cold-water stress-induced and(More)
Acute administration of 2-deoxy-D-glucose (2-DG), an antimetabolic glucose analogue induces a powerful analgesia which adapts following repeated administration. 2-DG analgesia displays significant cross-tolerance with morphine, and like morphine analgesia, is potentiated in hypophysectomized rats. The present study examined further the role of opiates in(More)
In addition to the well-known activation of the pituitary-adrenal axis, acute exposure to severe stressors includes a temporary analgesia in rats. Thus, the present study investigates whether the pituitary was involved in the mediation of analgesia induced by severe cold-water swim (CWS) stress. Flinch-jump thresholds were measured 30 min following 3.5-min(More)
In this investigation, rats subjected to swim stress showed within 24 hours significant increases in both the level of chromosome aberrations and Sister Chromatid Exchanges (SCEs) in bone marrow cells. The generality of cytogenetic damage by behavioral stressors was demonstrated by exposing rats to both cold-and warm-water forced swims, to white noise, and(More)
Antinociception, induced by continuous cold-water swims (CCWS) and certain parameters of inescapable foot shock, is reduced in hypophysectomized rats receiving supplements of corticosterone and l-thyroxine. To assess which lobe of the pituitary gland is involved in this effect, the first experiment compared the effects of total hypophysectomy and posterior(More)