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1.
J Exp Psychol Learn Mem Cogn ; 45(11): 1942-1954, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30816766

ABSTRACT

In the current research, we tested the idea that the proximity of contrasting categories in a learning sequence would determine the features to which participants attend in a categorization task. For the first experiment, we designed a 4-category structure in which pairs of categories could be perfectly distinguished using 1 feature. Two of the categories were paired together in the first part of the learning phase, followed by the other 2 categories in the second part of this phase. In a transfer test in which all 4 categories were shown, participants attended more to the features that differentiated the paired categories than to the other, equally diagnostic features. In the second experiment, we extended this finding to a task that involved all 4 categories but in which pairs of categories were more likely to be interleaved. Once again, participants were more likely to pay attention to the dimensions that separated the 2 categories in proximity in the sequence. These findings suggest that the local learning context influences the representation of a category. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Subject(s)
Concept Formation/physiology , Pattern Recognition, Visual/physiology , Serial Learning/physiology , Transfer, Psychology/physiology , Adult , Eye Movement Measurements , Humans , Young Adult
2.
Clin Radiol ; 70(12): 1382-7, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26392317

ABSTRACT

AIM: To evaluate the association of quantitative computed tomography (CT) measures of emphysema with the occurrence of pneumothorax after CT-guided needle lung biopsy (NLB) accounting for other risk factors. MATERIALS AND METHODS: One hundred and sixty-three CT-guided NLBs performed between 2008 and 2013 with available complete chest CT within 30 days were reviewed for the occurrence of post-procedure pneumothorax. Percent emphysema was determined quantitatively as the percentage of lung voxels below -950 HU on chest CT images using automated software. Multivariable regression was used to assess the association of percent emphysema volume with the occurrence of post-procedure pneumothorax. The association of percent emphysema volume with the pneumothorax size and need for chest tube placement after NLB was also explored. RESULTS: Percent emphysema was significantly associated with the incidence of post-NLB pneumothorax (OR=1.10 95% confidence interval: 1.01-1.15; p=0.03) adjusting for lower-lobe lesion location, needle path length, lesion size, number of passes, and pleural needle trajectory angle. Percent emphysema was not associated with the size of the pneumothorax, nor the need for chest tube placement after NLB. CONCLUSION: Percent emphysema determined quantitatively from chest CT is a significant predictor of post-NLB pneumothorax.


Subject(s)
Pneumothorax/diagnostic imaging , Pneumothorax/pathology , Radiography, Interventional , Biopsy, Needle/methods , Cross-Sectional Studies , Female , Humans , Image-Guided Biopsy/methods , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Risk Factors , Tomography, X-Ray Computed
3.
Mem Cognit ; 42(3): 508-24, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24217892

ABSTRACT

According to an influential multiple-systems model of category learning, an implicit procedural system governs the learning of information-integration category structures, whereas a rule-based system governs the learning of explicit rule-based categories. Support for this idea has come in part from demonstrations that motor interference, in the form of inconsistent mapping between response location and category labels, results in observed deficits, but only for learning information-integration category structures. In this article, we argue that this response location manipulation results in a potentially more cognitively complex task in which the feedback is difficult to interpret. In one experiment, we attempted to attenuate the cognitive complexity by providing more information in the feedback, and demonstrated that this eliminates the observed performance deficit for information-integration category structures. In a second experiment, we demonstrated similar interference of the inconsistent mapping manipulation in a rule-based category structure. We claim that task complexity, and not separate systems, might be the source of the original dissociation between performance on rule-based and information-integration tasks.


Subject(s)
Concept Formation/physiology , Learning/physiology , Task Performance and Analysis , Adult , Humans , Young Adult
4.
Autism Res ; 6(4): 280-7, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23512772

ABSTRACT

We tested the hypothesis that the direction of gaze of target faces may play a role in reported face recognition deficits in those with an autism spectrum disorder (ASD). In previous studies, typically developing children and adults better remembered faces in which the eyes were gazing directly at them compared with faces in which the eyes were averted. In the current study, high-functioning children and adolescents with an ASD and age- and IQ-matched typically developing controls were shown a series of pictures of faces in a study phase. These pictures were of individuals whose gaze was either directed straight ahead or whose gaze was averted to one side. We tested the memory for these study faces in a recognition task in which the faces were shown with their eyes closed. The typically developing group better remembered the direct-gaze faces, whereas the ASD participants did not show this effect. These results imply that there may be an important link between gaze direction and face recognition abilities in ASD.


Subject(s)
Child Development Disorders, Pervasive/psychology , Fixation, Ocular/physiology , Memory/physiology , Recognition, Psychology/physiology , Adolescent , Adult , Child , Face , Female , Humans , Male , Pattern Recognition, Visual/physiology , Photic Stimulation/methods , Young Adult
5.
J Exp Psychol Learn Mem Cogn ; 38(4): 860-80, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22746953

ABSTRACT

Studies of incidental category learning support the hypothesis of an implicit prototype-extraction system that is distinct from explicit memory (Smith, 2008). In those studies, patients with explicit-memory impairments due to damage to the medial-temporal lobe performed normally in implicit categorization tasks (Bozoki, Grossman, & Smith, 2006; Knowlton & Squire, 1993). However, alternative interpretations are that (a) even people with impairments to a single memory system have sufficient resources to succeed on the particular categorization tasks that have been tested (Nosofsky & Zaki, 1998; Zaki & Nosofsky, 2001) and (b) working memory can be used at time of test to learn the categories (Palmeri & Flanery, 1999). In the present experiments, patients with amnestic mild cognitive impairment or early Alzheimer's disease were tested in prototype-extraction tasks to examine these possibilities. In a categorization task involving discrete-feature stimuli, the majority of subjects relied on memories for exceedingly few features, even when the task structure strongly encouraged reliance on broad-based prototypes. In a dot-pattern categorization task, even the memory-impaired patients were able to use working memory at time of test to extract the category structure (at least for the stimulus set used in past work). We argue that the results weaken the past case made in favor of a separate system of implicit prototype extraction.


Subject(s)
Alzheimer Disease/psychology , Cognitive Dysfunction/psychology , Concept Formation , Learning , Memory, Short-Term , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Photic Stimulation
6.
Neurochem Int ; 53(6-8): 325-37, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18835309

ABSTRACT

The purpose of the present study was to determine whether the flavonoid, baicalin is effective at blunting the negative influence of ischemia/reperfusion to the rat retina in situ and of various insults to a transformed retinal ganglion cells (RGC-5 cells) in culture. Baicalin was administered intraperitoneally just before and after an ischemic insult to retina of one eye of a rat. Ischemia was delivered by raising the intraocular pressure above the systolic blood pressure for 50min. Seven days after ischemia, retinas were analysed for the localisation of various antigens. Retinal extracts were also analysed for various mRNAs. Moreover, the content of specific proteins was deduced in retinal and optic nerve extracts. Also, RGC-5 cells in culture were given one of three different insults, light (1000lx for 2 days), hydrogen peroxide (200microM H(2)O(2) for 24h) or serum deprivation (48h) where cell survival and reactive oxygen species (ROS) formation was assayed. Moreover, a lipid peroxidation assay was used to compare the antioxidant capacity of baicalin with the flavonoid, epigallocatechin gallate (EGCG). Ischemia/reperfusion to the retina affected the localisation of Thy-1 and choline acetyltransferase (ChAT) and the content of various proteins (optic nerve and retina) and mRNAs (retina). Importantly, baicalin statistically blunted most of the effects induced by ischemia/reperfusion. Only the increase in caspase-8 and caspase-3 mRNAs caused by ischemia/reperfusion were unaffected by baicalin treatment. Baicalin also attenuated significantly the negative insult of light, hydrogen peroxide and serum withdrawal to RGC-5 cells. In the lipid peroxidation studies, baicalin was also found to be equally effective as EGCG to act as an antioxidant. Significantly, the negative insult of serum withdrawal on RGC-5 cell survival was blunted by baicalin but not by EGCG revealing the different properties of the two flavonoids.


Subject(s)
Flavonoids/pharmacology , Hypoxia-Ischemia, Brain/drug therapy , Lipid Peroxidation/drug effects , Oxidative Stress/drug effects , Reperfusion Injury/drug therapy , Retinal Ganglion Cells/drug effects , Animals , Caspases/metabolism , Cell Survival/drug effects , Cell Survival/physiology , Cells, Cultured , Choline O-Acetyltransferase/metabolism , Culture Media, Serum-Free/toxicity , Hydrogen Peroxide/toxicity , Hypoxia-Ischemia, Brain/metabolism , Hypoxia-Ischemia, Brain/physiopathology , Injections, Intraperitoneal , Lipid Peroxidation/physiology , Neuroprotective Agents/pharmacology , Oxidative Stress/physiology , Photic Stimulation/adverse effects , Rats , Reactive Oxygen Species/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/physiopathology , Retinal Ganglion Cells/metabolism , Thy-1 Antigens/metabolism
7.
Graefes Arch Clin Exp Ophthalmol ; 245(9): 1335-45, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17265029

ABSTRACT

BACKGROUND: Diabetes inhibits dark adaptation and both processes alter the electroretinogram (ERG) in similar ways. This study aimed to investigate the relationship between oscillatory potentials (OPs) and the b-wave during dark adaptation and to determine if this relationship changes during the development of diabetes. METHODS: Twenty-one rats were assigned to adaptation, control and diabetic groups. Rats were dark adapted for periods between 20 minutes and 4 hours, and ERGs recorded. Diabetes was induced with streptozotocin, and ERGs measured after 3, 6, 9 and 12 weeks after injection. RESULTS: Increasing periods of dark adaptation led to a logarithmic increase in the amplitude of the b-wave and the OPs. This was accompanied by a decrease in the peak times of the OPs and b-wave. Total OP amplitude and b-wave amplitude were linearly related, allowing an empirical OP constant to be developed to describe the relationship between the two parameters. Diabetes led to a progressive decrease in the amplitude and increase in the peak time of all waves. The OP constant decreased in a linear fashion with increasing duration of diabetes. CONCLUSIONS: It is argued that OP masking of the b-wave could explain previous inconsistencies in reported ERG changes in diabetes and that a slowing of dark adaptation does not account for these ERG changes. The report concludes that the OPs and b-wave amplitudes and latencies are intimately related in the normal retina and that this correlation is lost predictably during the development of diabetes.


Subject(s)
Dark Adaptation/physiology , Diabetes Mellitus, Experimental/physiopathology , Diabetic Retinopathy/physiopathology , Retina/physiopathology , Animals , Blood Glucose/metabolism , Electroretinography , Male , Oscillometry , Perceptual Masking/physiology , Rats , Rats, Wistar , Time Factors
8.
Mem Cognit ; 35(8): 2088-96, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18265623

ABSTRACT

Recent research suggests that exemplar models of classification are disconfirmed by the finding of extreme prototype-enhancement effects and steep typicality gradients in a version of the prototype-learning paradigm. We argue that these results are due to learning-during-transfer effects and not to the abstraction of a prototype from the training instances. In the standard version of the paradigm, observers are flooded with multiple presentations of the prototype and its low distortions during transfer. In a modified transfer condition, we instead present multiple instances of an arbitrary high distortion and low distortions of that high distortion. An extreme "high-distortion enhancement effect" is observed. Also, there is a flattening of the typicality gradient associated with the standard patterns (prototype, low distortions, and standard high distortions). The results provide dramatic evidence of the role of learning during transfer in this task and force a reevaluation of the dominant current interpretation of the steep typicality gradient.


Subject(s)
Discrimination Learning , Orientation , Pattern Recognition, Visual , Perceptual Distortion , Problem Solving , Transfer, Psychology , Concept Formation , Humans , Judgment , Mental Recall , Probability Learning
9.
Mem Cognit ; 33(7): 1256-71, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16532858

ABSTRACT

Researchers have argued that an implicit procedural-learning system underlies performance for information integration category structures, whereas a separate explicit system underlies performance for rule-based categories. One source of evidence is a dissociation in which procedural interference harms performance in information integration structures, but not in rule-based ones. The present research provides evidence that some form of overall difficulty or category complexity lies at the root of the dissociation. The authors report studies in which procedural interference is observed for even simple rule-based structures under more sensitive testing conditions. Furthermore, the magnitude of the interference is large when the nature of the rule is made more complex. By contrast, the magnitude of interference is greatly reduced for an information integration structure that is cognitively simple. These results challenge the view that a procedural-learning system mediates performance on information integration categories, but not on rule-based ones.


Subject(s)
Attention , Comprehension , Decision Making , Mental Processes , Orientation , Pattern Recognition, Visual , Size Perception , Adult , Female , Humans , Male , Reaction Time , Transfer, Psychology
10.
Mem Cognit ; 32(3): 390-8, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15285123

ABSTRACT

Results from the classic dot pattern distortion paradigm have sometimes yielded prototype enhancement effects that could not be accounted for by exemplar models of categorization. However, in these experiments the status of the prototype was confounded with certain stimulus-specific properties as well as with the frequency of presentation of the prototype during testing. In two mock-subliminal experiments, participants made categorization judgments to patterns that were generated as prototypes, low-level distortions, or high-level distortions. The participants rated the prototypes as being more likely to be members of a category, although no patterns were presented during training, and there was no objective category structure. In two other experiments, greater prototype enhancement effects were observed when the prototype and low-level distortions were presented with greater frequency during transfer. These results suggest that classic prototype enhancement effects may not be due to the abstraction of a prototype at time of original learning, but rather to other factors not formalized in extant models.


Subject(s)
Judgment , Pattern Recognition, Visual , Humans , Models, Psychological , Random Allocation , Transfer, Psychology
11.
Psychon Bull Rev ; 11(6): 1048-54, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15875974

ABSTRACT

Most published studies of category learning in amnesia have reported intact categorization performance. These results have been used to challenge single-system accounts of categorization and recognition, in which a single representational system mediates performance in these two tasks. Many of the published studies, however, have shown a numerical advantage for controls over amnesics and often have had low statistical power. A meta-analysis was conducted to assess whether this numerical advantage is significant when the data are pooled across studies. This analysis indicates that amnesic subjects do, in fact, show deficits in categorization tasks, which is consistent with single-system exemplar model predictions.


Subject(s)
Amnesia/diagnosis , Judgment , Humans
12.
Mem Cognit ; 32(6): 916-31, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15673180

ABSTRACT

In three experiments, we examined the recognition of faces at novel orientations. Although performance tended to decay as difference between the study and the test angles increased, an orientation that was symmetric with respect to the study orientation showed strong performance--in many cases, better than the frontal view. We investigated the properties of this particular facility in perception and memory tasks. Symmetrized faces showed surprisingly different patterns of behavior than did unsymmetrized faces, despite the fact that many faces were already fairly symmetric. In memory experiments, the subjects showed robust symmetric orientation effects and could differentiate between the original study views and the symmetric orientation. In a third experiment, we demonstrated that smooth motion improved performance at the symmetric orientation, whereas two control motions did not. Together, the three experiments support the view that multiple representations are at work during the recognition of faces at the symmetric orientation and that, during memory tasks, subjects tend to rely on representations that are more robust against texture asymmetries and that may include limited depth information.


Subject(s)
Face , Motion Perception , Recognition, Psychology , Humans , Reaction Time
13.
J Exp Psychol Learn Mem Cogn ; 29(6): 1160-73, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14622053

ABSTRACT

In a recent article. J. P. Minda and J. D. Smith (2002; see record 2002-00620-002) argued that an exemplar model provided worse quantitative fits than an alternative prototype model to individual subject data from the classic D. L. Medin and M. M. Schaffer (1978) 5/4 categorization paradigm. In addition, they argued that the exemplar model achieved its fits by making untenable assumptions regarding how observers distribute their attention. In this article, we demonstrate that when the models are equated in terms of their response-rule flexibility, the exemplar model provides a substantially better account of the categorization data than does a prototype or mixed model. In addition, we point to shortcomings in the attention-allocation analyses conducted by J. P. Minda and J. D. Smith (2002). When these shortcomings are corrected, we find no evidence that challenges the attention-allocation assumptions of the exemplar model.


Subject(s)
Attention , Concept Formation , Decision Making , Discrimination Learning , Pattern Recognition, Visual , Problem Solving , Humans , Logic , Models, Psychological , Probability Learning , Transfer, Psychology
14.
J Exp Psychol Learn Mem Cogn ; 29(6): 1194-209, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14622055

ABSTRACT

In 2 sets of experiments, the authors investigated the basis for old-item distinctiveness effects in perceptual recognition, whereby distinctive old items are recognized with higher probability than are typical old items. In Experiment 1, distinctive old items were defined as those lying in isolated regions of a continuous-dimension similarity space. In this case, any beneficial effects of distinctiveness were absent or small, regardless of the structure of the test list used to assess recognition memory. In Experiment 2, distinctive items were defined as those objects containing certain discrete, individuating features. In this case, large old-item distinctive effects were observed, with the nature of the effects being modulated by the structure of the test lists. A hybrid-similarity exemplar model, combining elements of continuous-dimension distance and discrete-feature matching, was used to account for these distinctiveness effects in the recognition data.


Subject(s)
Attention , Discrimination Learning , Memory, Short-Term , Pattern Recognition, Visual , Color Perception , Concept Formation , Decision Making , Face , Humans , Judgment , Probability Learning , Reading , Verbal Learning
15.
J Int Neuropsychol Soc ; 9(3): 394-406, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12666764

ABSTRACT

Previous research has demonstrated dissociations between categorization and recognition performance in amnesic patients, supporting the idea that separate memory systems govern these tasks. However, previous research has also demonstrated that these dissociations are predicted by a single-system model that allows for reasonable parameter differences across groups. Generally, previous studies have employed categorization tasks that are less demanding than the recognition tasks. In this study, we distinguish between single-system and multiple-system accounts by testing memory-impaired individuals in a more demanding categorization task. These patients, just like previous amnesic participants, show a dissociation between categorization and recognition when tested in previously employed paradigms. However, they display a categorization deficit when tested in the more challenging categorization task. The results are interpreted as support for a single-system framework in which categorization and recognition depend on one representational system.


Subject(s)
Memory Disorders/physiopathology , Models, Psychological , Recognition, Psychology/physiology , Aged , Alzheimer Disease/physiopathology , Amnesia/physiopathology , Female , Geriatric Assessment , Humans , Male , Mental Recall , Pattern Recognition, Visual/physiology , Problem Solving , Retention, Psychology , Verbal Behavior/physiology , Verbal Learning
16.
Mem Cognit ; 30(6): 934-44, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12450096

ABSTRACT

Nosofsky and Zaki (2002) found that an exemplar similarity model provided better accounts of individual subject classification and generalization performance than did a mixed prototype model proposed by Smith and Minda (1998; Minda & Smith, 2001). However, these previous tests used a nonlinearly separable category structure. In the present work, the authors extend the previous findings by demonstrating a superiority for the exemplar generalization model over the mixed prototype model in a case involving a linearly separable structure. Because this structure has numerous features that Minda and Smith argued should be conducive to prototype-based processing, the results pose a significant challenge to the mixed prototype view.


Subject(s)
Learning , Models, Psychological , Generalization, Psychological , Humans
17.
J Exp Psychol Learn Mem Cogn ; 28(5): 924-40, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12219799

ABSTRACT

J. D. Smith and colleagues (J. P. Minda & J. D. Smith, 2001; J. D. Smith & J. P. Minda, 1998,2000; J. D. Smith, M. J. Murray, & J. P. Minda, 1997) presented evidence that they claimed challenged the predictions of exemplar models and that supported prototype models. In the authors' view, this evidence confounded the issue of the nature of the category representation with the type of response rule (probabilistic vs. deterministic) that was used. Also, their designs did not test whether the prototype models correctly predicted generalization performance. The present work demonstrates that an exemplar model that includes a response-scaling mechanism provides a natural account of all of Smith et al.'s experimental results. Furthermore, the exemplar model predicts classification performance better than the prototype models when novel transfer stimuli are included in the experimental designs.


Subject(s)
Attention , Generalization, Psychological , Generalization, Stimulus , Models, Psychological , Concept Formation , Discrimination, Psychological , Female , Forecasting , Humans , Male , Mental Processes , Mental Recall , Random Allocation , Reproducibility of Results , Transfer, Psychology
18.
Brain Res ; 862(1-2): 36-42, 2000 Apr 17.
Article in English | MEDLINE | ID: mdl-10799666

ABSTRACT

Age- and sex-matched pigmented (Lister Hooded) and albino (Wistar) rats were used in this study. The retinas of the animals were subjected to pressure-induced ischaemia (35 min, 120 mmHg) and reperfusion (3 days) in precisely the same way. The b-wave of the electroretinogram (ERG) in the pigmented animals recovered to normal levels while those of the albino rats were reduced by more than 80%. Moreover, the choline acetyltransferase (ChAT) immunoreactivity associated with a sub-set of amacrine cells was almost completely obliterated in the retinas from the albino rats but unaffected in the retinas of the pigmented rats. Also, in certain areas of the retina from albino rats there was a suggestion that the calretinin-immunoreactivity was affected. This was never seen in the retinas of the pigmented animals. The GABA-immunoreactivity in the retina of both albino and pigmented rats appeared to be unaffected by ischaemia/reperfusion. The data presented show that retinas from albino rats are more susceptible to ischaemia/reperfusion than retinas from pigmented animals. The results also show that reduction of the b-wave of the ERG and changes in the nature of the ChAT immunoreactivity represent sensitive markers to detect the effect of ischaemia/reperfusion to the retina.


Subject(s)
Albinism/physiopathology , Ischemia/physiopathology , Retina/pathology , Retinal Vessels/physiology , Age Factors , Albinism/pathology , Animals , Calbindin 2 , Choline O-Acetyltransferase/analysis , Electroretinography , Female , Ischemia/pathology , Pigments, Biological/physiology , Rats , Rats, Wistar , Retina/chemistry , Retina/enzymology , S100 Calcium Binding Protein G/analysis , gamma-Aminobutyric Acid/analysis
19.
Vision Res ; 39(24): 3995-4002, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10748932

ABSTRACT

Carotid artery occlusion (two vessel occlusion; 2-VO) for 3 or 9 months causes a suppression of the electroretinogram. However, after 3 months the retinal morphology appears unaffected judging from the localisation of GABA, ChAT, alpha PKC, Thy-1 and GFAP immunoreactivities. Moreover, no difference in NMDA-R1, opsin or Thy-1 mRNA levels were detected. In contrast, after 9 months 2-VO photoreceptor degeneration occurred as indicated by thinning of the outer nuclear layer and reduced Ret-P1 immunoreactivity. All other immunoreactivities appeared normal. These findings were supported by analysis of retinal mRNA levels. We conclude that the major effect of prolonged 2-VO is photoreceptor degeneration.


Subject(s)
Carotid Stenosis/pathology , Photoreceptor Cells, Vertebrate/pathology , Animals , Cell Death , Electroretinography , Rats , Rats, Wistar , Retina/pathology , Reverse Transcriptase Polymerase Chain Reaction
20.
Brain Res ; 768(1-2): 120-4, 1997 Sep 12.
Article in English | MEDLINE | ID: mdl-9369308

ABSTRACT

Studies on rat cortical cultures show that glutamate (10 microM) or hypoxia followed by reoxygenation causes damage to the cells as indexed by a release of lactate dehydrogenase (LDH). These effects could be counteracted by the N-methyl-D-aspartate (NMDA) antagonist MK-801 (2 microM) but not by the kainate/AMPA antagonist CNQX (100 microM). These data favour the view that the damage caused to the cells by glutamate and hypoxia/reperfusion is mediated via NMDA receptors. The damage to the cells could also be prevented by melatonin (100 microM). The melatonin effect is not mediated by specific receptors because it was not blunted by the melatonin antagonist, luzindole. Moreover, NMDA stimulated an accumulation of 45Ca2+ by cortical neurones, but although this effect was counteracted by MK-801, melatonin was ineffective, which showed that the neuroprotective effect of melatonin is not elicited by direct action with NMDA receptors. Ascorbate and iron stimulated the production of free radicals in a retinal cell preparation. Chelation of the iron with deferoxamine prevented this process as did melatonin while MK-801 had no effect. The combined findings suggest that melatonin counteracts the in vitro destructive effects of NMDA or hypoxia/reperfusion by preventing accumulation of excessive free radicals.


Subject(s)
Cerebral Cortex/drug effects , Hypoxia, Brain/prevention & control , Melatonin/pharmacology , N-Methylaspartate/pharmacology , Neurons/drug effects , Neuroprotective Agents/pharmacology , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Animals , Cells, Cultured , Cerebral Cortex/cytology , Cerebral Cortex/metabolism , Excitatory Amino Acid Antagonists/pharmacology , Hypoxia, Brain/metabolism , L-Lactate Dehydrogenase/metabolism , Neurons/metabolism , Oxygen/metabolism , Rats , Reactive Oxygen Species/metabolism
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