Biomedical subjects

F Josef van der Staay

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

8 recordsLinked to original sources

PubMed2006

Time-dependent involvement of cAMP and cGMP in consolidation of object memory: studies using selective phosphodiesterase type 2, 4 and 5 inhibitors.

The present study investigated the time-dependent memory enhancing properties of three selective phosphodiesterase inhibitors (PDE-I) vardenafil (PDE5-I), rolipram (PDE4-I) and BAY 60-7550 (PDE2-I) in the object recognition task. In particular, the time-dependent involvement of cAMP and cGMP in memory consolidation was assessed by altering the time points of drug administration. Vardenafil (1 mg/kg, p.o.), rolipram (0.03 mg/kg, i.p.), and BAY 60-7550 (3 mg/kg, p.o.) were tested in rats with a 24 h delay between the learning and the test trial. The PDE-Is were administered at different time points, i.e. directly after, 1 h, 3 h and 6 h after the first trial. Using a 24 h interval, vardenafil only showed an effect on object memory when injected directly after trial 1, rolipram only showed an improvement when injected 3 h after trial 1 and BAY 60-7550 improved memory when injected either directly after or 3 h after trial 1. No treatment effects were found when the compounds were administered 1 h or 6 h after the first trial. Our results extend our previous data that different types of PDE-Is affect different stages of memory consolidation. Moreover, the present study provides further support that selective PDE-Is can influence memory consolidation in a time-dependent manner, assumingly by elevating central cAMP and cGMP levels.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2006

Animal models of behavioral dysfunctions: basic concepts and classifications, and an evaluation strategy.

In behavioral neurosciences, such as neurobiology and biopsychology, animal models make it possible to investigate brain-behavior relations, with the aim of gaining insight into normal and abnormal human behavior and its underlying neuronal and neuroendocrinological processes. Different types of animal models of behavioral dysfunctions are reviewed in this article. In order to determine the precise criteria that an animal model should fulfill, experts from different fields must define the desired characteristics of that model at the neuropathologic and behavioral level. The list of characteristics depends on the purpose of the model. The phenotype-abnormal behavior or behavioral dysfunctions-has to be translated into testable measures in animal experiments. It is essential to standardize rearing, housing, and testing conditions, and to evaluate the reliability, validity (primarily predictive and construct validity), and biological or clinical relevance of putative animal models of human behavioral dysfunctions. This evaluation, guided by a systematic strategy, is central to the development of a model. The necessity of animal models and the responsible use of animals in research are discussed briefly.

Animals↗

PubMed2006

Two months makes a difference in spatial orientation learning in very old FBNF1 rats.

Age-related changes in cognitive performance may be more pronounced in the period near or exceeding the median life span. Therefore, we compared the acquisition of a Morris water escape task by two groups of very old Fischer344 x Brown Norway hybrid rats. The mean age difference between the two groups of rats (a 33- to 34-month-old group versus a 35- to 36-month-old group) was about 2 months. Both groups of rats initially had the same level of performance, but then the younger group learned to escape onto the submerged platform faster, swimming a shorter distance, than the older group. By the fifth acquisition session, the younger rats needed only half the time and swam a shorter distance before they reached the platform than the older rats. These differences in learning were not due to different locomotor abilities as both groups had a similar swimming speed. These results suggest that age-related changes in cognitive performance are indeed more pronounced in the period around the median life span. We also discussed different set-ups to perform cross-sectional age-comparison studies. If there are not sufficient animals from one batch, it may be worthwhile to combine animals from different batches per age group, provided that breeding, rearing, housing, and testing conditions are highly standardized.

Aging↗

PubMed2006

Long-term effects of immunotoxic cholinergic lesions in the septum on acquisition of the cone-field task and noncognitive measures in rats.

In rats, nonspecific mechanical or neurotoxic lesions of the septum impair spatial memory in, e.g., Morris water- and radial-maze tasks. Unfortunately, the lack of specificity of such lesions limits inferences about the role of the cholinergic hippocampal projections in spatial cognition. We therefore tested the effects of septal lesions produced by 192 IgG-saporin in rats, which is highly selective for basal forebrain cholinergic neurons, on home cage activity, noncognitive tests (modified Irwin test, open field and forced swimming tests, and various sensorimotor tasks), and the cone-field spatial learning task. The immunotoxic lesion reduced acetylcholine (ACh) levels in the septum (-61%) and hippocampus (>-75%). Rats with lesions showed mild home-cage hyperactivity at 4 weeks postlesion, but no noncognitive deficits at 13 weeks postsurgery. In the cone-field task, rats with septal lesions made more working- and reference-memory errors than the controls, but acquisition curves were parallel in both groups. The speed of visiting cones was faster in the rats with lesions, indicative of disturbed attention or increased motivation. These data support the growing evidence that involvement of the septohippocampal cholinergic system in spatial learning and memory may have been overestimated in studies that used lesions with poor selectivity.

Acetylcholine↗

PubMed2005

Rats with scopolamine- or MK-801-induced spatial discrimination deficits in the cone field task: animal models for impaired spatial orientation performance.

Spatial cognition appears to be compromised in elderly and in patients suffering from dementia. These deficits are believed to be modelled, at least partly, by the administration of scopolamine or MK-801 in normal adult animals. In order to establish an animal model suited for the evaluation of putative cognition enhancers, we assessed the effects of scopolamine (0.3, 0.5, 0.7 mg kg(-1), i.p.) and MK-801 (0.07, 0.08, 0.09 mg kg(-1), s.c.) in rats trained in the cone field. This task allows the simultaneous investigation of working memory (WM), reference memory (RM) and search strategies. Scopolamine and MK-801 reliably induced spatial cognition deficits in the cone field without inducing behavioural side effects. This task appears to be suited for assessing the effects of putative cognition-enhancing compounds on spatial cognition.

Animals↗

PubMed2005

Effects of the cholinesterase inhibitors donepezil and metrifonate on scopolamine-induced impairments in the spatial cone field orientation task in rats.

The aim of these experiments was to assess whether the clinically validated cognition enhancers donepezil (Aricept, E2020) and metrifonate antagonize scopolamine-induced deficits in the cone field, a complex spatial discrimination task. The cone field task allows measurement of the effects of experimental manipulations on working and reference memory (WM and RM), search strategies, and on the speed and latency to execute the task. The effects of a single administration of donepezil (0.1, 0.3, and 1.0 mg kg(-1), p.o.) and metrifonate (30, 60, and 120 mg kg(-1), p.o.) were investigated in adult Harlan-Wistar rats trained to a stable level of performance and pretreated with scopolamine (0.5 mg kg(-1), i.p. 30 min before training). Scopolamine impaired WM without inducing overt non-cognitive side-effects. Donepezil did not antagonize the scopolamine-induced deficits, whereas metrifonate antagonized the WM deficits at the dose of 60 mg kg(-1), but not at 30 or 120 mg kg(-1). Thus, a cholinesterase inhibitor with proven clinical efficacy can antagonize scopolamine-induced spatial memory deficits. The cone field would be a useful component of a behavioral screening battery to test the effects of putative cognition enhancers.

Animals↗

PubMed2004

Delayed non-matching to position performance in aged hybrid Fischer 344 x brown Norway rats: a longitudinal study.

In this study, the effects of aging on the performance in a delayed non-matching to position (DNMTP) task were investigated longitudinally in hybrid Fischer 344 x Brown Norway rats. The rats were first trained to perform the task. Subsequently, their performance was assessed monthly from 28 to 34 months of age. The measures of responding on the DNMTP schedule did not decrease in the course of the study. After the last DNMTP test, choline acetyltransferase (ChAT) activity and glial fibrillary acidic protein (GFAP) content were measured in frontal cortex and hippocampus. We found that higher levels of GFAP in the frontal cortex, but not hippocampus, were associated with a poorer performance in the DNMTP task. Our findings support the notion that repeated testing prevents the age-related decline in cognitive functions that has been reported in cross-sectional studies. Pathology of the frontal cortex seems to predict a faster rate of forgetting in aging rats.

Age Factors↗

PubMed2002

Assessment of age-associated cognitive deficits in rats: a tricky business.

Every living organism is affected by changes as a consequence of aging. Perhaps the most appropriate concept to describe age-related changes is that of 'functional age'. Laboratory rodents are especially suited as models of cognitive aging in humans, because they have a relatively short life-span and because many tests have been developed to investigate their cognitive performance. Examples from studies using the Morris water escape task were chosen to describe and discuss factors which must be considered before drawing conclusions about age-related cognitive deficits. In particular, the roles of rearing and housing conditions, of sensorimotor impairments, and of motivational differences between young and old rats are discussed. Conclusions are drawn about how aging studies should be conceived and performed.

Aging↗