Biomedical subjects

T Steckler

Publications and source records attributed to T Steckler.

47 records · Page 3Linked to original sources

PubMed1995

Do differences in visuospatial ability between senile dementias of the Alzheimer and Lewy body types reflect differences solely in mnemonic function?

Visuospatial memory was investigated in two groups of patients suffering from senile dementias of the Alzheimer (SDAT) or Lewy body (SDLT) types; a, third, age-matched, healthy control group was also included. The two patient groups were mildly demented and could not be distinguished from each other by traditional tests of cognitive function. A different pattern of performance emerged in the two groups on a computerised test of spatial working memory, which is a self-ordered pointing task requiring the subject to search for hidden tokens. An analysis of the pattern of errors revealed that the SDLT group made more of both possible types of error ("Within Search" and "Between Search") than the SDAT group. Neither patient groups' performance differed from each other when assessed on a computerised Corsi spatial span task. A measure of planning ability was obtained by examining search strategies. Although an index previously developed to measure the subject's use of a particular strategy in the spatial working memory task failed to detect any differences between the three groups, a novel index was calculated which focuses on performance within a search, and this revealed deficits in both demented groups. Since the two patient groups differed from each other in the spatial working memory, but not the Corsi spatial span, task, it is suggested that the differences between the two demented groups are not due to a specific mnemonic impairment, but reflect dysfunctions in non-mnemonic processes mediated by fronto-subcortical circuits, which are more severely damaged in SDLT.

Aged↗

PubMed1994

Lesions of the pedunculopontine tegmental nucleus do not alter delayed non-matching to position accuracy.

The cholinergic pedunculopontine tegmental nucleus, located in the brainstem, and part of the reticular formation, has traditionally been linked to motor function, sleep and arousal, but has recently been implicated in cognition. To investigate this possibility, rats with radiofrequency lesions were tested on a delayed non-matching to position task, a test for spatial recognition memory abilities. Data were analysed according to the methods of signal detection theory. Lesions of the pedunculopontine nucleus did not produce marked deficits in accuracy, although there was some evidence to suggest that motivational processes could have been affected.

Acetylcholine↗

PubMed1994

The pedunculopontine tegmental nucleus: a role in cognitive processes?

The cholinergic pedunculopontine tegmental nucleus, located in the brainstem and part of the reticular formation, has been traditionally linked to motor function, arousal and sleep. Its anatomical connections, however, raise the possibility that the pedunculopontine tegmental nucleus is also involved in other aspects of behaviour such as motivation, attention and mnemonic processes. This is of obvious importance, since the pedunculopontine tegmental nucleus undergoes degeneration in human neurodegenerative disorders also characterized by attentional and/or mnemonic deficits. Moreover, recent behavioural animal work suggests that cognitive processes may be represented in the pedunculopontine tegmental nucleus. The difficulty that faces research in this area, however is the possible influence of cognition by other processes, such as arousal state, motivation and motor function. Nevertheless, by reviewing the literature, the pedunculopontine tegmental nucleus seems to be involved in attentional and possibly also in learning processes. These processes could be mediated by influencing cortical function via the thalamus, basal forebrain and basal ganglia. The involvement of the pedunculopontine tegmental nucleus in mechanisms of memory, however, seems to be rather unlikely.

Animals↗

PubMed1994

TouchWindows and operant behaviour in rats.

We describe a new method which has the potential to assess a wide range of behavioural, especially cognitive, processes in rats. This involves the presentation of microcomputer-generated visual stimuli on a standard video monitor, with the rat responding on a transparent pressure-sensitive device (TouchWindow) placed directly in front of it. The method allows a large variety of visual stimuli to be used, with responses possible over the entire area of the window. In this report, we describe the basic design of the equipment and the training protocol and present behavioural data from a light-tracking (visual attention) task.

Animals↗

PubMed1994

Sympathomimetic drug abuse masking an endogenous hyperadrenergic state, Graves' disease.

Sympathomimetic drug use or abuse in a thyrotoxic individual can be clinically devastating as a result of enhanced cellular sensitivity to adrenergic stimulation. Thus, it is critical to recognize thyrotoxicosis in a patient with coexistent sympathomimetic drug abuse. This case report describes a patient with Graves' disease and severe hyperadrenergic symptomatology that was thought to result from sympathomimetic drug abuse.

Adolescent↗

PubMed1993

Human platelet 5-HT2 receptor binding sites re-evaluated: a criticism of current techniques [corrected].

The human platelet 5-HT2 receptor may resemble a peripheral model of central 5-HT2 binding sites and has been linked to changes in 5-HT2 receptor function in depression. Therefore, evaluation of the human platelet 5-HT2 binding characteristics is important. Comparing [3H]ketanserin and [3H]LSD as ligands clearly indicated [3H]LSD as ligand of choice for binding studies dealing with the human platelet 5-HT2 receptor. [3H]LSD binding was specific, saturable, and depended upon incubation time, protein concentration and previous handling of tissue, i.e., use of fresh or frozen tissue. In contrast, studies with [3H]ketanserin were unsatisfactory. Although mean receptor densities and affinities have been relatively constant between individuals and over time in healthy subjects with [3H]LSD, examination of the individual data showed considerable variations within single subjects. Thus, KD ranged between 0.50 and 0.68 nM, and Bmax was in the range of 64.9 to 97.1 fmol/mg protein in healthy individual subjects. Therefore, we recommend [3H]LSD as ligand of choice to study platelet 5-HT2 receptor binding in humans. Furthermore, repeated measurement of individual data over time should be interpreted cautiously, especially when data from depressed patients are under examination.

Adult↗

PubMed1993

Effects of NBM lesions with two neurotoxins on spatial memory and autoshaping.

Four groups of Wistar rats received either vehicle, quisqualate, or one of two different ibotenic acid infusions into the basal forebrain. Following recovery from surgery, all rats were tested in three distinct behavioral paradigms: the Bättig radial arm maze, the Barnes circular platform, and autoshaping in an operant chamber. The results showed that the size and site of the ibotenic acid lesion had a profound effect on acquisition performance in some, but not all, procedures. Performance in the Bättig maze and acquisition of a food-rewarded lever press were in particular disrupted by ibotenic acid lesions. The severity of the reduction in cortical choline acetyltransferase (ChAT) did not correlate with performance in the tests. Quisqualate produced the largest reduction in ChAT levels but had no significant effect on performance in any of the three procedures used. Anatomic analysis revealed severe nonspecific damage to the striatum following ibotenic acid that was more pronounced in the group receiving a highly concentrated solution of ibotenic acid as compared to rats infused with a greater volume but less concentrated solution of the neurotoxin. Striatal damage was much less severe following quisqualic acid infusions. However, both types of neurotoxins produced equivalent nonspecific degeneration of the reticular thalamic nucleus. These data confirm reports that nonspecific damage appears to define the severity of ibotenic acid lesions on subsequent behavioral performance.

Animals↗

PubMed1993

[Are phase II or phase II antidepressive drug studies still feasible considering currently required inclusion and exclusion criteria?].

The present policy of pharmaceutical companies to aim at perfectionistic, and therefore inflexible protocols for clinical drug-trials renders patient recruitment increasingly difficult or even impossible, and may result in an increasing number of non-completed studies. It appears that many of today's inclusion and exclusion criteria are not sufficiently assessed in terms of their scientific basis and clinical usefulness. Sense and nonsense of these criteria are discussed. The tendency to adhere to streamlined protocols to certify the needs of drug regulators will severely impair the feasibility and validity of antidepressant drug trials in psychiatric in-patients.

Adolescent↗

PubMed1989

Spontaneous exploration of a 6-arm radial tunnel maze by basal forebrain lesioned rats: effects of the benzodiazepine receptor antagonist beta-carboline ZK 93 426.

Nine days following ibotenic acid induced basal forebrain lesions or a sham-operation, rats were allowed to explore an automated six-arm radial tunnel maze. From each session, several measures of locomotor and exploratory activity were registered. Lesioned and sham-operated animals were treated with either the benzodiazepine receptor antagonist beta-carboline ZK 93 426 (5 mg/kg; IP) or vehicle (Cremofor EL 10% in saline; IP; n = 10 for each group). Treatment was carried out 30 min before each session during acquisition (seven sessions) and reversals of the maze configuration (seven sessions). Eight days following the 14th session, the animals were retested without any further drug treatment. The main results suggest that the lesion resulted in locomotor hyperactivity, an increase in the number of blind arm entries, and of choice stereotypy. Treatment with ZK 93 426 attenuated the lesion-induced alterations of locomotor and exploratory activities. During the retest, the lesioned, previously vehicle-treated rats revisited arms which they had already explored during this session more frequently than the lesioned, previously ZK-treated rats; the latter group did not differ from the sham-lesioned controls. It is concluded that basal forebrain lesioned animals explored the tunnel maze less efficiently than sham-lesioned controls and that the lesioned animals benefited from the treatment with ZK 93 426. Although the specificity of the lesion in terms of destruction of cholinergic neurons remains unsettled, and although the psychological significances of the behavioral measures obtained from the tunnel maze are not yet fully understood, these results suggest that antagonists or partial inverse agonists at the benzodiazepine receptor may be able to normalize basal forebrain lesion-induced behavioral alterations.

Animals↗

PubMed1989

2-[3H]deoxyglucose uptake patterns in rats exploring a six-arm radial tunnel maze: differences between experienced and nonexperienced rats.

In an automated tunnel maze, rats were allowed to explore either a 6-arm radial configuration ("experienced") or an alley maze configuration ("nonexperienced"). The activity of control rats was restricted to the center of the maze. After 8 daily sessions and a 5-day break, catheters were implanted into the jugular vein. Two days later, 2-deoxyglucose was administered before both experimental groups were exposed to the 6-arm radial configuration. Nonexperienced rats differed from experienced rats in terms of efficiency of exploration, but not in locomotor activity. Compared with experienced animals, nonexperienced rats showed an increase in 2-deoxyglucose uptake in prefrontal and cingulate cortices and in mediodorsal and laterodorsal thalamic nuclei. Exposure of rats to familiar and unfamiliar maze patterns resulted in different patterns of brain metabolic activity.

Animals↗

PubMedDate not supplied

Effects of the monoamine oxidase A inhibitor moclobemide on hippocampal plasticity in GR-impaired transgenic mice.

A reduction in glucocorticoid receptor (GR) function leads to hippocampus-dependent allocentric spatial learning deficits, altered novelty exploration and disrupted hippocampal long-term potentiation (LTP) in transgenic mice expressing a GR antisense construct. After continuous long-term treatment of these mice with moclobemide (a reversible inhibitor of monoamine oxidase A), spatial navigation performance but not accuracy improved during initial acquisition. These changes were associated with a shift of the threshold for the induction of hippocampal LTP at low stimulation frequencies. Moreover, novel object exploration increased in both control and transgenic animals following long-term treatment with moclobemide. These findings open the possibility that antidepressants might improve hippocampal function under conditions of impaired stress hormone regulation, and that these drugs might in part act through this mechanism to attenuate cognitive deficiency in disorders such as depression.

Animals↗