PubMed Health⌕ Search

Biomedical subjects

F Boon

Publications and source records attributed to F Boon.

At least 19 recordsLinked to original sources

Ethanol impairs behavioral strategy use in naive rats but does not prevent spatial learning in the water maze in pretrained rats.

RATIONALE: Ethanol impairs performance in the water maze in rats. A detailed behavioral analysis is required to fully evaluate the nature of the impairment. OBJECTIVES: A detailed behavioral analysis was carried out to evaluate the effect of ethanol on performance in the water maze task in male hooded rats given 2.0 or 6.0 g/kg ethanol by gavage. Multiple measures of water maze strategies learning and spatial learning were studied. METHODS: Water maze trials were recorded on videotape and digitized for offline analysis. Some rats were naive at the start of spatial training, whereas other rats received water maze strategies pretraining prior to spatial training to familiarize them with the general behavioral strategies required in the task. RESULTS: Naive ethanol-treated rats exhibited both spatial learning and water maze behavioral strategies impairments. There was no evidence of a spatial learning impairment that was independent of an associated behavioral strategies impairment. Further, ethanol impaired the ability of naive rats to swim to a stable visible platform. Pretrained ethanol-treated rats performed significantly better than naive ethanol-treated rats on almost all measures, and were indistinguishable from controls on most measures. CONCLUSIONS: These results suggest that ethanol may impair water maze performance in naive rats by interfering with their ability to acquire and use required water maze behavioral strategies and generate adaptive swim paths. Ethanol does not prevent robust spatial learning in rats that are familiar with required water maze behavioral strategies.

Animals↗

Individual and combined manipulation of muscarinic, NMDA, and benzodiazepine receptor activity in the water maze task: implications for a rat model of Alzheimer dementia.

Recent evidence indicates that Alzheimer disease typically involves different degrees of impairment in a variety of neurotransmitter systems, behaviors, and cognitive abilities in different patients. To investigate the relations between neurotransmitter system, behavioral, and cognitive impairments in an animal model of Alzheimer disease we studied spatial learning in a Morris water maze in male Long-Evans rats given neurochemical agents that targeted muscarinic cholinergic, NMDA, or benzodiazepine systems. Naive rats given a single agent or a combination of agents were severely impaired in place responding and had behavioral strategy impairments. Rats made familiar with the required water maze behavioral strategies by non-spatial pretraining performed as well as controls if given a single agent. Non-spatially pretrained rats with manipulation of both muscarinic cholinergic and NMDA or muscarinic cholinergic and benzodiazepine systems had a specific place response impairment but no behavioral strategy impairments. The results suggest that impairment of both muscarinic cholinergic and NMDA, or muscarinic cholinergic and benzodiazepine systems may model some aspects of human Alzheimer disease (impairments in navigation in familiar environments), but not other aspects of this disorder (global dementia leading to general loss of adaptive behavior). Previous research suggests that impairment of both muscarinic cholinergic and serotonergic systems may provide a better model of global dementia. The water maze testing and detailed behavioral analysis techniques used here appear to provide a means of investigating the contributions of various combinations of neurotransmitter system impairments to an animal model of Alzheimer disease.

Alzheimer Disease↗

Behavioral effects of anti-muscarinic, anti-serotonergic, and anti-NMDA treatments: hippocampal and neocortical slow wave electrophysiology predict the effects on grooming in the rat.

Previous research has shown that hippocampal and neocortical activation accompanies the postural changes occurring during self-grooming in rats but is absent or reduced during the stereotyped components of grooming, including head-washing and licking or biting. Since electrocortical activation is dependent on ascending cholinergic and serotonergic projections, we hypothesized that central muscarinic and serotonergic blockade would disrupt grooming by degrading cerebral control of changes in posture. Consistent with this, we find that systemic injections of scopolamine: (a) markedly reduce the occurrence of adaptive changes in posture during grooming; (b) reduce the probability of transitions from head-washing to body grooming; (c) reduce both the probability and duration of sequences of body grooming; and (d) do not affect the duration of head-washing or the probability of transitions from washing the snout to washing over the top of the head. Destruction of central serotonergic neurons with intracerebral injections of 5,7-dihydroxytryptamine increases the tendency of scopolamine to shorten the duration and increase the number of separate sequences of grooming. Systemic injections of a NMDA antagonist (CGS 19755) also impair grooming behavior. The data show that blockade of muscarinic and glutamatergic transmission impairs instinctive behavior as well as learned behavior and that the behavioral effects of muscarinic and serotonergic blockade are consistent with data obtained from the study of cortical slow wave electrophysiology.

5,7-Dihydroxytryptamine↗

Complex behavioral strategy and reversal learning in the water maze without NMDA receptor-dependent long-term potentiation.

Successful performance of the water maze task requires that rats learn complex behavioral strategies for swimming in a pool of water, searching for and interacting with a hidden platform before its spatial location can be learned. To evaluate whether NMDA receptor-dependent long-term potentiation (NMDA-LTP) is required for learning the required behavioral strategies, rats with NMDA-LTP blocked by systemic pharmacological treatment were trained in the behavioral strategies using simplified and stepwise training methods. Despite the blockade of NMDA-LTP in the dentate gyrus and hippocampal area CA1, rats learned the required behavioral strategies and used them to learn both initial and reversed platform locations. This is the first evaluation of the role of NMDA-LTP specifically in behavioral strategy learning. Although hippocampal NMDA-LTP might contribute to the water maze task, this form of LTP is not essential for learning complex behavioral strategies or multiple hidden platform locations.

Animals↗

Expression of Epstein-Barr virus latent genes and adhesion molecules in AIDS-related non-Hodgkin's lymphomas: correlation with histology and CD4-cell number.

In patients with the acquired immunodeficiency syndrome, the incidence of non-Hodgkin's lymphoma is increased. Two major subgroups of AIDS-related NHL (ARL) have been defined: Burkitt-type NHL (BL) and polymorphic centroblastic/immunoblast-rich large cell lymphomas (CB/IB LCL). These subgroups differ in their association with the Epstein-Barr virus (EBV) and thus possibly in their pathogenesis. We studied the expression of EBER (EBV small RNA's), and EBV latent antigens LMP-1 and EBNA-2 in 43 cases of ARL and related this to histology and immune status (CD4-cell count). In addition, in 19 cases the expression of adhesion molecules (LFA-1 (CD18), ICAM-1 (CD54), alpha4beta1 integrin (CD49d/CD29), L-selectin (CD62L) and CD44) was studied. We found major differences between the two subgroups. Patients with BL had significantly higher CD4-cell counts; only 40% of their lymphomas were EBV-positive, and when EBV-positive, were of the type I latency phenotype. Expression of adhesion molecules important for immune recognition was absent or low in all BL. In contrast, the majority of CB/IB LCL were EBER-positive (79%). 58% of EBV-positive LCL (particularly those in patients with CD4-cell counts below 0.2 x 10(9)/1) had a type II or III latency phenotype. Most LCL showed expression of LFA-1, ICAM-1 and alpha4beta1 integrin. CD44s expression was restricted to CB/IB LCL, in whom high expression of the metastasis-associated exon v6-containing CD44 variant was also observed. The observed EBV-latency types and full expression of adhesion molecules suggest that defective Epstein-Barr virus immunity is important in the pathogenesis of CB/IB large cell lymphomas.

CD18 Antigens↗

Testing hypotheses of spatial learning: the role of NMDA receptors and NMDA-mediated long-term potentiation.

The role of NMDA receptors and NMDA-mediated hippocampal long-term potentiation (LTP) in spatial learning was studied in rats using the competitive, systemically administered NMDA receptor antagonists CGS19755 ((+/-)-cis-4-phosphonomethyl-2-piperidine carboxylic acid) and NPC17742 (2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid). CGS19755 caused sensorimotor disturbances and disrupted acquisition of the water maze in naive rats. The sensorimotor disturbances were greatly reduced and maze learning was normal in spite of the blockade of dentate gyrus LTP by CGS19755 in rats that had first been familiarized with the general task requirements by non-spatial pretraining. In a second experiment, antagonism of NMDA receptors caused small, but reliable, impairments in Y-maze and visible platform visual discrimination tasks. The results indicate that NMDA receptors are not crucial for water maze acquisition using a spatial learning strategy, and that NMDA antagonists cause visual and other sensorimotor disturbances in naive rats that could help account for their poor performance in this task.

Amino Acids↗

The effects of a single neonatally induced convulsion on spatial navigation, locomotor activity and convulsion susceptibility in the adult rat.

The effect of a single neonatal convulsion on subsequent behaviour was investigated in the male rat. Convulsions were induced by heat or pentylenetetrazol on days 1, 10 or 21. As adults, locomotor activity, spatial ability and convulsion susceptibility were measured. Significant differences were seen in some measures and some groups but a single neonatal convulsion did not induce a consistent and significant pattern of behavioural change, despite the persistent change in hippocampal physiology shown in a previous study.

Aging↗

Detailed behavioral analysis of water maze acquisition under APV or CNQX: contribution of sensorimotor disturbances to drug-induced acquisition deficits.

N-methyl-D-aspartate (NMDA) receptor antagonists disrupt acquisition of the water maze and cause sensorimotor disturbances. In a detailed behavioral analysis in male rats, it was found that the NMDA antagonist DL-2-aminophosphonovaleric acid (APV) caused sensorimotor disturbances in behaviors required for maze performance and that these correlated with acquisition impairments in both hidden and visible platform versions of the maze. Behavioral disturbances included thigmotaxic swimming, swimming over and deflecting off the platform, abnormal swim behavior, and hyperactivity. Rats familiar with the behavioral strategies involved in the task performed normally under APV. The results are consistent with the known role of NMDA receptors in sensorimotor mechanisms and suggest that drug-induced sensorimotor disturbances contributed to poor acquisition scores in naive rats. NMDA may contribute to but does not appear to be essential for spatial learning in the water maze.

2-Amino-5-phosphonovalerate↗

Detailed behavioral analysis of water maze acquisition under systemic NMDA or muscarinic antagonism: nonspatial pretraining eliminates spatial learning deficits.

A detailed behavioral analysis of water-maze acquisition showed that the N-methyl-D-aspartate (NMDA) antagonist NPC17742 and the muscarinic antagonist scopolamine caused sensorimotor disturbances in behaviors required for maze performances and that these correlated with acquisition impairments in both hidden and visible platform versions of the maze in male rats. Behavioral disturbances included thigmotaxic swimming, swimming over and deflecting off the platform, abnormal swim behavior, and hyperactivity. Rats familiar with the behavioral strategies involved in the task performed normally under NPC17742 or scopolamine. The results indicated that drug-induced sensorimotor disturbances contributed to poor acquisition scores in naive rats. NMDA or muscarinic activity may contribute to but do not appear to be essential for spatial learning in the water maze.

Amino Acids↗

[Autologous bone marrow transplantation in the treatment of children with neuroblastoma; 30 patients in 10 years].

OBJECTIVE: To evaluate the role of high dose chemotherapy and autologous bone marrow transplantation (ABMT) in children with metastasized neuroblastoma (stage IV) in partial or complete remission. DESIGN: Retrospective analysis. SETTING: The former Emma Child Hospital and the Academic Medical Center, Amsterdam. METHOD: In the period January 1980 to May 1991, ABMT was used in 30 children (mean age 3 years) with a neuroblastoma stage IV treated with chemotherapy. Occurrence of fever, infections, haemorrhagic diathesis, mucositis, ileus and the duration of hospital stay were measured as indications of illness. The mean weight loss and the duration of aplasia were also measured. RESULTS: Eight of 30 patients stayed alive until June 1993. Three patients died within 1 month after start of treatment. The median survival of the other 19 patients was 15 months. The mean weight loss was 7.6% and the period of aplasia had a mean duration of 18-20 days. Two-year disease free survival was 26.6% with a median follow-up of 118.5 months (29-150).

Antineoplastic Agents↗

Brain temperature- and behavior-related changes in the dentate gyrus field potential during sleep, cold water immersion, radiant heating, and urethane anesthesia.

The field potential evoked in the dentate gyrus (DG) by stimulation of the perforant path (PP) is known to vary with ongoing behavior and with brain temperature. To further study these phenomena chronic stimulating and recording electrodes were implanted into the PP and DG of rats, and a thermistor was implanted into the contralateral homotopic DG. Field potentials and brain temperature records were made during (1) slow wave sleep (SWS), (2) radiant heating, (3) immersion in cool water, (4) a control session during which no manipulations were made, and (5) under urethane anesthesia. In another group of rats field potentials were recorded during (1) baseline immobile wakefulness, (2) SWS, (3) before SWS or after gentle awakening from SWS (eyes open and presence of intermittent slow waves in the EEG), (4) immobile wakefulness, and (5) 24 h later. Findings were that field EPSP slope decreased and population spike (PS) amplitude increased by up to 60% of baseline values during conditions in which brain temperature was reduced (SWS, immersion in cool water, urethane anesthesia). Conversely, EPSP slope increased and PS amplitude decreased by up to 100% of baseline values during conditions in which brain temperature increased (awakening from SWS, radiant heating, and warming after immersion in cool water or urethane anesthesia). Product moment correlations between brain temperature and field potential measures confirmed the statistical reliability of these findings and accounted for up to 77% of the variance. These findings confirm the robust effect on hippocampal field potentials of brain temperature changes due to exogenous heating and cooling, and extend this effect to anesthetic- and sleep-induced brain temperature changes. They also identify a state that behaviorally resembles quiet wakefulness but resembles SWS in terms of neocortical EEG, brain temperature, and hippocampal field potential measures. The findings indicate the need to control for brain temperature-mediated changes in hippocampal research that uses the dentate gyrus field potential as a dependent measure.

Analysis of Variance↗

Persistent physiological effects caused by a single pentylenetetrazol induced seizure in neonatal rats.

A single seizure was induced by pentylenetetrazol (PTZ; 150 mg/kg i.p.) in 1-day-old and 21-day-old rats; control littermates were given saline (i.p.) injections. In vitro recordings were made in hippocampal slices derived from adult (2-3.5-month-old) rats. The population responses in CA1, CA3 and dentate gyrus (DG) were recorded following double-pulse stimulation of Schaffer collateral (CA1 stratum radiatum, for CA1 and CA3 recordings) and perforant path (for DG recordings). Paired-pulse stimuli at an interpulse interval (IPI) of 10-200 ms and intensity of 1.5, 2 or 4 times the stimulus threshold were used. PTZ given on day 1 resulted in a highly significant increase in the paired-pulse facilitation (PPF) of the population EPSP, but not of the population spike, in CA1 at all stimulus intensities. In the DG, PPF of both the population EPSP and population spike was found at 1.5 x threshold intensity. PTZ given on day 21 decreased PPF of the population EPSP and spike in CA1 and had no significant effect in the DG. No significant difference was found in CA3 responses after seizures on day 1 or day 21. The slices from seized and control animals were not different in their stimulus thresholds or response to a single pulse. It is concluded that a single neonatal PTZ-induced seizure had long-lasting physiological consequences which depend on the age of seizure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

An examination of the relations between hippocampal long-term potentiation, kindling, afterdischarge, and place learning in the water maze.

Two approaches were used to study the relations between the acquisition of place learning in the Morris water maze and long-term potentiation (LTP), kindling, and afterdischarge (AD). In the first, the possibility of behavioral LTP in the dentate gyrus field potential evoked by stimulation of the perforant path was evaluated in rats that showed robust place learning in the water maze. There was no effect of place learning on the field potential, and field potential measures did not correlate with place learning acquisition measures. In the second approach, the effect of bilateral saturation of LTP on subsequent place learning in the water maze task, begun within 5 minutes of the last LTP session, was evaluated. The effect of kindled seizures evoked bilaterally from the perforant path, or of a single unilateral AD, on acquisition of the water maze task (begun within 10 minutes) were also evaluated. Bilateral LTP saturation did not affect place learning, and the bilateral LTP group learned as readily as controls. In contrast, the kindled and AD groups were severely impaired in their performance of the place learning task. A second day of training in the water maze without any further electrical stimulation indicated that these groups had acquired considerable information on the first day of maze training and were not distinguishable from controls on the second day of training. This indicated that the deficit in these groups on the first day of training was temporary and likely resulted from a temporary perturbation of normal brain function due to the seizures. The results indicate that bilateral saturation of LTP in the dentate gyrus does not affect place learning in the water maze. They also indicate that recent hippocampal seizures, but not kindling, disrupt place learning in this task.

Animals↗

Evidence for different neurochemical contributions to long-term potentiation and to kindling and kindling-induced potentiation: role of NMDA and urethane-sensitive mechanisms.

Long-term potentiation (LTP) and kindling share a number of features, and it has been suggested that LTP might constitute the cellular mechanism of kindling. This question was approached by assessing the effect of urethane anesthesia (0.75 or 1.5 g/kg) or blockade of NMDA receptors by local infusion of DL-2-amino-5-phosphonovaleric acid (APV; 7.5 micrograms) on LTP, partial kindling, and kindling-induced potentiation (KIP) in the perforant path-dentate gyrus circuit of the intact hooded rat. Urethane anesthesia attenuated but did not block LTP and completely blocked partial kindling and KIP. APV completely blocked LTP but did not block partial kindling or KIP in the unanesthetized rat. These results suggest that different neurochemical mechanisms can support LTP on the one hand, and kindling and KIP on the other. They are consistent with a contribution by NMDA-mediated LTP to kindling and KIP, but they indicate that this contribution is not crucial for kindling and KIP in this circuit.

2-Amino-5-phosphonovalerate↗

Rapid and reliable induction of partial status epilepticus in naive rats by low-frequency (3-Hz) stimulation of the amygdala.

Naive rats were electrically stimulated in the amygdala with biphasic square wave pulses at 3 Hz in a model of partial status epilepticus (SE). This treatment led to the rapid kindling of seizures in all rats, and the subsequent induction of SE in 100% of rats stimulated for approximately 30-60 min. Extensive gliosis and degeneration was seen in the basal forebrain of the SE brains. This method of inducing SE is simpler, more rapid, and more reliable than similar methods reported previously.

Amygdala↗