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1.
A great deal is now known about the mechanisms of conditioned fear acquisition and expression. More recently, the mechanisms
of inhibition of conditioned fear have become the subject of intensive study. The major model system for the study of fear
inhibition in the laboratory is extinction, in which a previously fear conditioned organism is exposed repeatedly to the fear-eliciting
cue in the absence of any aversive event and the fear conditioned response declines. It is well established that extinction
is a form of new learning as opposed to forgetting or “unlearning” of conditioned fear, and it is hypothesized that extinction
develops when sensory pathways conveying sensory information to the amygdala come to engage GABAergic interneurons through
forms of experience-dependent plasticity such as long-term potentiation. Several laboratories currently are investigating
methods of facilitating fear extinction in animals with the hope that such treatments might ultimately prove to be useful
in facilitating exposure-based therapy for anxiety disorders in clinical populations. This review discusses the advances that
have been made in this field and presents the findings of the first major clinical study to examine the therapeutic utility
of a drug that facilitates extinction in animals. It is concluded that extinction is an excellent model system for the study
of fear inhibition and an indispensable tool for the screening of putative pharmacotherapies for clinical use. 相似文献
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In Alzheimer's disease (AD), pathological changes are found in the basal forebrain cholinergic system (BFCS), serotonergic raphe (RA), and noradrenergic locus coeruleus (LC) systems. The present study was designed to determine the extent to which selective damage in each of these systems individually could produce an impairment of memory, one of the clinical symptoms of AD. Rats were given selective lesions by injecting ibotenic acid into the nucleus basalis magnocellularis and medial septal area (i.e., BFCS); 5,7-dihydroxytryptamine into the medial and dorsal RA; and 6-hydroxydopamine (6-OHDA) into the LC or by ip injections of (2-chloroethyl)N-ethyl-2-bromobenzylamine HCl (DSP4). Levels of choline acetyltransferase (ChAT), norepinephrine, and serotonin verified lesion effectiveness and selectivity. Chronic changes in serotonergic-2 and beta-adrenergic receptors were also determined. Rats were tested in a delayed spatial alternation in a T-maze. BFCS lesions impaired choice accuracy with intertrial delays of 5, 30, and 60 s. RA lesions or DSP4 injections impaired choice accuracy only when the intertrial delay was 60 s. LC lesions (by 6-OHDA) did not impair choice accuracy at any delay. The results suggest that the pathological changes in the BFCS and RA are sufficient to produce the types of memory impairments associated with dementia, but the quantitative effects of pathology in these two systems are different. 相似文献
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Maroya Spalding Walters Nandini Sreenivasan Bobbie Person Mark Shew Daniel Wheeler Julia Hall Linda Bogdanow Karyn Leniek Agam Rao 《American journal of public health》2015,105(11):2256-2261
Objectives. Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures.Methods. We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno.Results. Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno.Conclusions. Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks.Botulism is a rare but serious illness that can lead to respiratory failure and death. Botulism patients may initially present with blurred or double vision, drooping eyelids, slurred speech, and difficulty swallowing before developing more severe signs and symptoms, such as paralysis and difficulty breathing. In the United States, an average of 145 confirmed botulism cases are reported each year, of which approximately 15% are attributable to foodborne botulism.1 Foodborne botulism is caused by ingestion of botulinum toxin, a bacterial toxin that is produced under the following rarely attained conditions: an anaerobic environment with warm temperatures and low acid, salt, and sugar concentrations.2 Alaska Native foods and home-canned vegetables are the food items most commonly associated with foodborne botulism3,4; however, in the past decade, 5 foodborne botulism outbreaks have been attributed to pruno, an illicit alcoholic beverage made in prisons.5 Pruno was initially recognized as a botulism vehicle after it was implicated in 2 outbreaks in California in 2004 and 2005; these outbreaks resulted in confirmed botulism in 5 inmates, 3 of whom were critically ill and mechanically ventilated.6 No additional outbreaks were reported until 2011, when 8 maximum security inmates in Utah developed botulism after drinking pruno. Three were mechanically ventilated, and most reported persistent symptoms, such as weakness, 11 months after the outbreak.7 The following year, 12 Arizona inmates were sickened in 2 outbreaks of botulism associated with pruno consumption; 8 were mechanically ventilated.5 In all 5 outbreaks, pruno was made with potatoes,5 an uncommon pruno ingredient according to online sources, and a food historically associated with botulism.8,9 Because of these outbreaks, pruno-related botulism accounted for 40% and 48% of foodborne botulism cases in the United States in 2011 and 2012, respectively (Centers for Disease Control and Prevention, unpublished data).Internet sources indicate that pruno is common in US prisons.10–12 Although recent trends suggest future pruno-related botulism outbreaks are likely to occur,5,7 there is a dearth of information about how pruno is made and distributed in prisons, and the social and entrepreneurial aspects of its production and use. To address these gaps and inform botulism outbreak prevention measures, 4 months after the Utah outbreak, we conducted a qualitative inquiry in the affected prison to better understand the brewing process, social context of pruno, and communication strategies for informing inmates about the risk of botulism from pruno. 相似文献
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