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F J van der Staay

Publications and source records attributed to F J van der Staay.

14 recordsLinked to original sources
PubMed1995

General pharmacology of the putative cognition enhancer linopirdine.

The putative cognition enhancer linopirdine (3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one, CAS 105431-72-9) is supposed to act by enhancing the release of neurotransmitters, especially acetylcholine. The present study assessed the effects of a single administration of this compound on the central nervous system in eight different rat and mouse models (CNS general pharmacology). In each test performed, linopirdine was administered subcutaneously in doses of 3, 10, and 30 mg/kg. The compound did not affect traction ability and nociceptive responsiveness nor did it induce catalepsy. Linopirdine impaired motor coordination in the balance rod test. The compound showed a distinct proconvulsive action in the pentylenetetrazole threshold dose test and induced in the highest dose tested (30 mg/kg) lethal seizures in some mice. It increased the duration of hexobarbital-induced anaesthesia in mice. Rats treated with linopirdine showed ptosis, salivation, slight sedation, paw beating and slight hypothermia. These results support the hypothesis that linopirdine acts by elevating the release of different neurotransmitters such as acetylcholine and dopamine. The compound has a low potential to produce side effects at pharmacodynamic active doses.

Animals↗
PubMed1994

The effects of chronic treatment with a calcium channel antagonist on two types of generalized epilepsies in rats.

Although calcium antagonists possess antiepileptic properties in various models of epilepsy, their role after chronic administration and in models for generalized absence epilepsy has not been studied. Twenty-four male Wistar rats, aged 84-94 weeks, were chronically provided with EEG electrodes. Two groups received dietary nimodipine (860 ppm) for 14 and 21 weeks, respectively, while a control group received the same rat chow without nimodipine. The EEG was recorded for 3 h to establish the effects of nimodipine on spike-wave discharges. Next, 50 mg/kg pentylenetetrazol (PTZ) was injected to establish the effects on convulsive epilepsy, and the EEG was recorded for 30 min. All animals had spontaneous spike-wave discharges (SWD), but there were no differences between the three groups. However, chronic nimodipine treatment had a significant effect on PTZ-induced seizures: the group that had been treated with nimodipine for 21 weeks showed significantly more and longer-lasting seizures than the control group. The facilitating effects of chronically administered of nimodipine on PTZ-induced seizures are striking and opposite to those reported in the literature. In a second study, nimodipine was administered acutely, but no effects of nimodipine on PTZ-induced epilepsy could be detected. It can be concluded that chronic dietary administration of a calcium antagonist induces different effects on PTZ-induced seizures than acute administration in aged Wistar rats with spontaneous occurring SWD.

Animals↗
PubMed1993

Effects of age on water escape behavior and on repeated acquisition in rats.

The standard water escape task in a circular pool measures predominantly spatial reference memory (RM). We first tested 3- and 24-month-old Wistar rats (WISW:Bor) in the standard task. The RM performance of the 24-month-old animals was impaired in comparison to that of the 3-month-old rats. In a second experiment, we compared the performance of 24-month-old rats with that of 3-month-old animals, using the repeated acquisition paradigm originally described by Whishaw (Physiology and Behavior, 35, 139-143, 1985; Behavioral Brain Research, 24, 59-72, 1987). In this paradigm, the decrease in escape latency from the first to the second trial within trial pairs measures predominantly spatial working memory (WM). The young rats acquired the task within the first sessions. In contrast, the 24-month-old animals did not acquire the task, even after 12 daily training sessions. It is not clear, however, whether the poor performance of the old rats on the repeated acquisition task reflects impaired WM or whether they did not acquire the procedural aspects of the task.

Age Factors↗
PubMed1992

Effects of chronic dietary choline on temporal discrimination of BN and WAG rats.

Using rats of the inbred BN and WAG strain, we tested the hypothesis that chronic dietary choline supplementation would especially affect the timing behavior of BN rats because of their lower cholinergic activity and their poor performance in aversively motivated learning and memory tasks. An apparent effect of chronic choline supplementation (2.5 mg choline chloride per ml water) on DRL-8" responding was not confirmed in a second experiment when the choline concentration was doubled. WAG rats treated chronically with choline showed a poorer temporal discrimination performance on a DRL-16" schedule than untreated WAG rats. In contrast, choline supplementation never had an effect on the performance of BN rats. The results of the DRL-16" experiment provide partial support for a hypothesis proposed by Church and Meck that the remembered time of reinforcement is inversely related to the functional activity of brain cholinergic activity: acetylcholine precursor treatment increases memory storage speed, which results in an overestimation of the time elapsed. An alternative explanation, which takes into account the aberrant EEG activities of WAG rats, is also discussed.

Acetylcholine↗
PubMed1992

Chronic dietary choline enrichment affects DRL responding of old, but not of adult CPBB rats.

Using adult (11-month-old) and aged (22-month-old) inbred female CPBB rats, we tested the hypothesis that chronic dietary choline supplementation affects timing behavior. The rats had received choline chloride in their tap water for about 9 months before they acquired responding on a differential reinforcement of low-rate schedule with a critical delay of 8 s (DRL-8"). One retention session and two extinction sessions were given 4 weeks after the end of acquisition. The treatment had no effect on the timing behavior of the adult rats. Choline-treated old animals made more perservation errors, i.e., responses with interresponse times (IRTs) < 2 s, than the untreated old control rats. Even after correction for burst responses, the frequency of short IRTs was higher in the treated than in the control group, indicating that choline supplementation slightly impaired timing behavior. The mechanisms underlying the action of supplemented choline are still unknown.

Aging↗
PubMed1991

Spatial memory processing during hippocampal long-term potentiation in rats.

It was investigated in rats whether hippocampal long-term potentiation (LTP) influences working and/or reference memory processing in the radial maze. After preliminary training to an intermediate level of performance, experimental subjects received a series of high-frequency trains of electrical pulses applied to the right perforant path. Two control groups were adopted in order to control for possible effects of stimulation plus operation, and operation alone, respectively. Twenty-four hours after the experimental treatment, animals were administered one trial of radial maze training. This sequence of hippocampal stimulation and radial maze training was replicated 15 times. After a retention interval of 2 months, one radial maze trial was presented on each of 3 consecutive days. The analysis of field potential data showed that periodic LTP stimulation produced a state of hippocampal LTP confined to the initial portion of the acquisition phase. Evaluation of radial maze data revealed a marginal improvement of working memory performance in the experimental group during the rising phase of hippocampal LTP.

Animals↗
PubMed1990

Genetic correlations in validating emotionality.

Sixty-six rats of seven inbred strains were observed in an open field (OF) and in a light-dark preference box (LDB). Each set of apparatus provides measures of locomotor activity and of the time spent in the "most protected" area (the corners in the OF, the dark compartment in the LDB). These measures are proposed to be indices of emotionality. In the present study, the reliability and validity of the OF and LDB measures were determined by genetic correlations. Genetic correlations (rGEN) within and between tests were used as they provide a more coherent picture of reliability and validity of the measures than product-moment correlations (rPM), since rGEN's are appropriate estimates of "true" individual scores. It appeared that the activity measure in the OF and the occupancies of the most protected parts of OF and LDB were valid indices of emotionality, while the activity measure in the LDB was not. We recommend that the occupancy measures in the OF and the LDB should be used in addition to the commonly used activity measure in the OF to assess emotionality. The results indicate that genetic correlations provide a useful tool to validate measures in animal research. The only experimental manipulation in this approach consists of using the variation between inbred strains.

Animals↗
PubMed1990

Differential effect of acetyl-l-carnitine on open field behavior in young and old rats.

Acetyl-l-carnitine (ALCAR) exerts antiaging effects with study we evaluated the effect of a chronic treatment with ALCAR (6 weeks, 50 mg/kg/day) on the open field behavior of 5-month-old and 26-month-old male Wistar rats. Old rats defecated more, made fewer crossings, and spent more time in the corner squares. However, it is difficult to interpret these findings in terms of an increase in emotional reactivity with age because locomotor performance generally has been found to be impaired in old rats. Consequently, treatment effects were analysed within age groups. ALCAR had no effect in young rats, but the old ALCAR-treated rats ambulated less and spent more time in the corner squares than the old control rats. We have interpreted this in terms of an enhanced emotional reactivity of old ALCAR-treated rats.

Acetylcarnitine↗
PubMed1990

The effects of aging in rats on working and reference memory performance in a spatial holeboard discrimination task.

The effects of aging on spatial memory performance of rats was studied in a holeboard task in which 4 of 16 holes were baited with food. Brown-Norway rats of five ages (4, 13, 19, 25, and 30 months) received a total of 80 acquisition trials. A clear age-related decline of spatial working and reference memory performance was found. The decline was most profound between 19 and 25 months of age. The speed of visiting holes and the development of a preferred pattern of hole-visits did not influence spatial discrimination performance. Correlational analysis supported the view that the working and reference memory measures represent distinct aspects of spatial memory.

Aging↗
PubMed1990

The cone field: a spatial discrimination task for the automatic and simultaneous assessment of working and reference memory in rats.

A cone field apparatus was developed in which spatial working memory (WM) and reference memory (RM) can be assessed automatically and simultaneously. The cone field is a large open field with 16 cones in it. A configuration of four cones was baited with a food pellet. In the holeboard, the predecessor of the cone field, no clear criteria exist to distinguish between accidental and directed orientations toward the target (hole). In the cone field the visit to the target (cone) is unambiguously defined. We found that senescent rats were impaired on both the WM and the RM. The development of a fixed pattern of visiting the baited cones was effectively prevented by starting the rats randomly from four different positions. When only one start position was used, rats developed a fixed pattern of visiting the baited cones. This pattern was more pronounced in the young than in the senescent animals. In the last experiment we explored whether the task might be suited for the assessment of WM and RM performance in longitudinal studies. Rats performed like naive animals on both memory components when re-acquisitions were separated by 4-month intervals without training.

Aging↗
PubMed1989

Selective fimbria lesions impair acquisition of working and reference memory of rats in a complex spatial discrimination task.

It has been reported that transections of the fimbria-fornix or lesions of the hippocampus selectively impair spatial working memory. Disruptive effects of these lesions on reference memory performance, however, have also been reported. We studied the effects of selective fimbria lesions on the acquisition of a complex spatial discrimination in the cone field. The cone field task is a place learning task that permits the simultaneous assessment of working and reference memory performance. Reproducible bilateral stereotaxic lesions were made by knife-cuts parallel to the midline. Sham lesions consisted of similar knife-cuts that were restricted to the overlying tissue. The rats were randomly started from 1 of 4 positions in order to prevent the development of a fixed food search pattern. On both memory components, fimbria-lesioned rats made about twice as many errors as the sham-lesioned and intact subjects, even after extensive training. Transection of the fimbria caused pronounced cholinergic denervation, predominantly at the more ventral part of the hippocampus, as indicated by reduced acetylcholinesterase histochemistry. Our results suggest a major role of the cholinergic innervation of the ventral hippocampus in spatial discrimination.

Acetylcholinesterase↗
PubMed1989

Spatial memory in rats: a cross validation study.

Two experiments were performed to investigate whether two measures of spatial memory, working memory (WM) and reference memory (RM), can be generalized over learning situations. In the first experiment, outbred WU rats were used; in the second four inbred strains. In both experiments rats were given 50 training trials in both a holeboard and a high-sided radial maze: 4 out of 16 holes and 4 out of 8 arms were baited. The number of WM (revisits to baited holes/arms) and RM (visits and revisits to never baited holes/arms) errors were calculated for 5 blocks of 10 trials; odd-even reliabilities were determined for the last 20 trials and were shown to be satisfactory for both measures in both types of apparatus. Error-decrements were analyzed by trend components. For both WM and RM, simple and canonical correlations were determined between means and significant trends in maze and holeboard as a test for construct validity; in both experiments r's and Rr's were very low. It was concluded that the concepts WM and RM are not validly generalizable over tests.

Animals↗
PubMed1981

A searching procedure for transformations and models in a classical Mendelian cross breeding study.

Adopting Wright's four criteria (homogeneity, normality, additivity of effects, and parsimony of parameters needed) concerning a good scale of measurement, a systematic procedure is presented to find an adequate transformation for the data of a classical Mendelian cross. By using Cavalli's least-squares fitting procedure, fits of all possible genetical (sub)models are compared to each other. The model yielding the best fit with as few parameters as possible is selected. More complex models are accepted only if they fit significantly better than simpler ones. Four worked examples are presented from a classical cross study in rats: time till onset of a learned bar-press response under a continuous-reinforcement schedule and protein content, acetylcholinesterase activity, and butyrylcholinesterase activity in the occipital cortex. Using several transformations, invariance of resulting models was found if the criterion of homogeneity of variance was met.

Animals↗