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Biomedical subjects

A Sahgal

Publications and source records attributed to A Sahgal.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1993

Lack of effect of dorsomedial thalamic lesions on automated tests of spatial memory in the rat.

The effects of cytotoxic lesions of nucleus medialis dorsalis on tests of spatial memory were examined in the rat. Extensive lesions of the nucleus did not impair either the acquisition or the subsequent performance of an automated test of working memory, delayed nonmatching-to-position. Detailed analysis of the animals' performance over varying retention delays failed to reveal any evidence of a deficit. The same animals performed normally in a spatial discrimination task and its subsequent reversals. The present results can be contrasted with those from animals with hippocampal system damage.

Animals↗
PubMed1993

The contribution of the anterior thalamic nuclei to anterograde amnesia.

This paper first reviews the anatomical, pathological, and neuropsychological evidence implicating the anterior thalamic nuclei in memory processes. It is concluded that there is much indirect evidence indicating that anterior thalamic dysfunction is an important factor in anterograde amnesia. More direct evidence for the involvement of the anterior thalamic nuclei in memory processes emerges from two experiments with rats that examined performance of a spatial test of working memory, delayed nonmatching-to-position. The first study revealed that neurotoxic lesions of the anterior thalamic nuclei and radiofrequency lesions of the fornix both produce equivalent performance deficits. In contrast, lesions of the mamillary bodies were without effect. A second study showed that lesions of the fornix and removal of the hippocampus produced very similar deficits. These data indicate that while the involvement of the anterior thalamic nuclei in certain memory functions depends on inputs from the hippocampus, this involvement need not depend on indirect afferents via the mamillary bodies.

Amnesia↗
PubMed1993

Combined serotonergic-cholinergic lesions do not disrupt memory in rats.

Rats were trained on a delayed nonmatching to position task, divided into four groups and given the following lesions: (a) SHAM (vehicle injection into nucleus basalis magnocellularis (NBM) and raphé nuclei (RN), (b) RN (5,7-dihydroxytryptamine lesions of raphé, vehicle into NBM), (c) NBM (quisqualic acid lesion of NBM, vehicle into RN), and (d) COMB (lesions of both RN and NBM). RN lesions had no effect on performance measures including accuracy (percent correct), errors of omission, bias, latencies, and magazine response rate. NBM lesions produced delay-independent (nonmnemonic) disruptions, but performance improved over the 20 days' test. The effects of COMB lesions were no worse than NBM lesions alone. The results suggest that (a) the serotonergic system is not essential for performance in this task, (b) NBM lesions transiently impair nonmnemonic aspects of performance, and (c) serotonergic-cholinergic interactions may not be essential for some cognitive processes.

5,7-Dihydroxytryptamine↗
PubMed1992

Removal of the hippocampus and transection of the fornix produce comparable deficits on delayed non-matching to position by rats.

Rats with radiofrequency lesions of the fimbria/fornix or with extensive aspiration lesions of the hippocampal region (the hippocampus proper, dentate gyrus, and subicular complex) were tested on their performance of a delayed non-matching to position task which had been learnt before surgery. On a given trial, one of two sample levers was presented in a random manner. Following a response on this lever and a subsequent delay, both levers were presented and reward was now contingent on a response on the lever that was not used as the sample. Both lesions produced equivalent performance deficits on this test of spatial working memory, the pattern of these deficits being consistent with a mnemonic impairment. The lack of difference between these two groups on a variety of performance measures indicates that hippocampal connections passing through the fornix are not only necessary for this test, but that non-fornical hippocampal connections appear unable on their own to maintain accurate responding.

Animals↗
PubMed1992

Matching-to-sample deficits in patients with senile dementias of the Alzheimer and Lewy body types.

Using a computerized matching-to-sample task, nonverbal visual recognition memory was studied in two groups of patients suffering from senile dementia of the Alzheimer type or the recently described senile dementia of the Lewy body type. The patients' cognitive abilities had been shown to be similar according to a number of standard psychometric tests. The two groups did not differ with respect to simultaneous matching-to-sample performance, although both were impaired relative to control. The group with senile dementia of the Lewy body type was severely impaired, relative to the group with senile dementia of the Alzheimer type, when delays (delayed matching to sample) were introduced. The findings suggest that short-term mnemonic processes, mediated by temporal lobe structures, could be more severely affected in senile dementia of the Lewy body type.

Aged↗
PubMed1992

Examination of parameters influencing [3H]MK-801 binding in postmortem human cortex.

[3H]MK-801 binding was used as an index of the glutamate receptor N-methyl-D-aspartate-subtype channel to examine the influence of gender, age, mode of death (agonal status), interval between death and autopsy (postmortem delay), and time in storage at -70 degrees C in well washed homogenate preparations from postmortem human frontal cortex. Basal binding and the modulatory effects of glutamate, glycine, spermidine, and zinc were examined with respect to these variables. Basal binding was sensitive to agonal status, being higher in sudden death cases. The effect of added glutamate and glycine was sensitive to age, with a trend toward lower binding with increasing age. The effect of added spermidine alone was sensitive to storage time at -70 degrees C, the binding being higher with longer storage time. The effect of added zinc was also sensitive to postmortem delay, with zinc causing a greater reduction in binding with shorter postmortem delays. Thus, with the exception of gender, all variables examined influenced [3H]MK-801 binding, highlighting the attention that should be given to these factors in postmortem studies in normal and diseased human subjects.

Aged↗
PubMed1991

Both fornix and anterior thalamic, but not mammillary, lesions disrupt delayed non-matching-to-position memory in rats.

Rats with radiofrequency lesions of the fimbria/fornix, or neurotoxic lesions of the mammillary bodies or the anterior thalamic nuclei were tested on their ability to perform a delayed non-matching-to-position task that had been learnt before surgery. In this task rats had to respond to a sample lever in an operant chamber and, after a variable delay (during which they were required to respond at the magazine tray), press the other lever when both were presented. Extensive mammillary body lesions had no effect on performance. In contrast, lesions in either the anterior thalamic nuclei or the fimbria/fornix produced marked deficits, the pattern of these deficits being consistent with a mnemonic impairment. It is argued that the anterior thalamic nuclei represent an important hippocampal output for spatial problems, but that the mammillary bodies are only necessary for certain types of mnemonic task.

Animals↗
PubMed1991

Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer's and Parkinson's diseases.

The binding of the selective 5-HT2 antagonist [3H]ketanserin has been investigated in the temporal cortex of patients with Alzheimer's disease (SDAT), Parkinson's disease (PD), senile dementia of Lewy body type (SDLT) and neuropathologically normal subjects (control). 5-HT2 binding was reduced in SDAT, PD with dementia and SDLT. SDAT showed a 5-HT2 receptor deficit across most of the cortical layers. A significant decrease in 5-HT2 binding in the deep cortical layers was found in those SDLT cases without hallucinations. SDLT cases with hallucinations only showed a deficit in one upper layer. There was a significant difference in cortical layers III and V between SDLT without hallucinations and SDLT with hallucinations. The results confirm an abnormality of serotonin binding in various forms of dementia and suggest that preservation of 5-HT2 receptor in the temporal cortex may differentiate hallucinating from non-hallucinating cases of SDLT.

Aged↗
PubMed1990

Opposing effects of vasopressin on matching versus non-matching to position: further evidence for response, not memory, modulation.

Rats were trained on either of two related variants of an operant memory task. In the matching to position (MTP) task, one of two retractable response levers appeared, at random, as the sample. A response caused the lever to retract and this was followed by a delay (0-32 s) interval, during which the subjects had to approach and respond at the magazine tray. Both levers were then presented and the rat had to respond, for food reward, to the one which had appeared as the sample. A second group of rats learned non-matching to position (NMTP). This task was very similar to MTP, with one crucial difference: here, the subject had to respond to the lever which had not appeared as the sample. Both groups of rats learned their respective tasks rapidly, performance depending on the delay interval as expected. They were then injected, peripherally, with different doses of arginine-vasopressin (AVP: 0-25 micrograms/kg), a peptide which others have argued improves mnemonic performance. There was evidence to suggest that MTP performance was improved by AVP; on the other hand, NMTP performance appeared to be disrupted. It is suggested that AVP induces a bias towards responding on one side of the two lever test chamber. In other words, it affects motor or motivational, not mnemonic mechanisms.

Animals↗
PubMed1990

Memory following cholinergic (NBM) and noradrenergic (DNAB) lesions made singly or in combination: potentiation of disruption by scopolamine.

Groups of rats were trained on either delayed matching or nonmatching to position tasks, then divided into four subgroups and given the following bilateral lesions: (a) SHAM [vehicle injection into the nucleus basalis magnocellularis (NBM) and dorsal noradrenergic bundle (DNAB)], (b) DNAB (6-hydroxydopamine lesion of the DNAB, vehicle into the NBM), (c) NBM (quisqualic acid lesion of the NBM, vehicle into the DNAB) and (d) DUAL (neurotoxin lesions of both DNAB and NBM). Following postoperative recovery, the DUAL lesion subjects were slightly impaired, but by the seventh day of testing all groups were performing at similar levels. This strongly suggests that quisqualate lesions of the NBM are not sufficient to produce severe and lasting mnemonic disorders resembling those seen in Alzheimer's disease (AD). These data also indicate that the noradrenergic system may not be of critical importance with respect to cognition. It was reasoned that an additional anticholinergic treatment might exacerbate an underlying deficiency. All groups were injected, peripherally, with the cholinergic antagonist scopolamine (0-0.5 mg/kg). This drug dose-dependently disrupted performance in all groups. Moreover, the highest dose had a marked effect in the DUAL group, impairing performance even when no mnemonic burden was present (at zero delay). The results suggest that cholinergic NBM and noradrenergic DNAB lesions produce only transient mnemonic deficiencies. A combination of the two can be disruptive, but longer term task (or reference) memory is the primary process affected, and only under certain conditions. The implication of these findings to research concerning animal models relating to Alzheimer's disease is discussed.

Animals↗
PubMed1989

[D-TRP11]-neurotensin, unlike alpha-flupenthixol, may not block amphetamine-induced hyperactivity in rats.

Recent reports have suggested that neurotensin (NT) and some of its analogues resemble neuroleptics, for example alpha-flupenthixol (FLU), in their ability to suppress locomotor activity. The results obtained support this conclusion, but only if total photocell counts (the "traditional" index) are considered. An improved method of measuring activity--where subjects have to interrupt photocell beams in sequence before a ("conditional") count is registered--suggested, in direct contrast to the total counts index, that the stable analogue of neurotensin [D-Trp11]-neurotensin (DTNT) increased activity slightly (Sahgal and Keith, 1986). The present report is on the effects of DTNT (0-8 microgram/rat, i.c.v.) and FLU (0-1 mg/kg, i.p.) on hyperactivity induced by D-amphetamine (1.5 mg/kg, i.p.). The usual total counts index of activity suggested that FLU and DTNT blocked the increase. On the other hand, conditional count data suggested that only FLU was effective. Both measures indicated that FLU and amphetamine, administered separately, suppressed and enhanced activity, respectively. In contrast, DTNT at these doses had no significant effect on the conditional counts but markedly suppressed total counts. Subsequent observation of DTNT-treated rats placed in small open fields, suggested that the peptide induced marked circling (ambulatory) behaviour, at the cost of other behavioural categories, especially rearing and grooming. It is argued that (a) DTNT may not resemble neuroleptics in its effects on motor behaviour and (b) conditional activity counts, and also measures relating to brief interruptions of photocell beams, can provide useful additional information concerning motor activity.

Amphetamine↗
PubMed1988

Vasopressin and amphetamine, but not desglycinamide vasopressin, impair positively reinforced visual attention performance in rats.

Rats were trained to respond to the lever above which a light stimulus was briefly (0.5 s) presented at unpredictable times. Once the task had been learned to criterion, subjects were injected, intra-peritoneally, with arginine8-vasopressin, desglycinamide arginine8-vasopressin (AVP or DGAVP: 0, 5, 10 or 20 micrograms/kg) or D-amphetamine (AMP: 0, 0.75, 1.5 or 3 mg/kg) prior to test. Attention performance was assessed using several different indices, including percent corrects, sensitivity and responsivity measures derived from signal detection theory, the recently described probability of (response) repetition and switching, and latency to respond. AVP had a disruptive effect on percent corrects at the highest dose and increased response latencies, but DGAVP, which lacks pressor activity, had no behavioral effects. AMP markedly impaired most aspects of performance, and was the only substance to alter response strategies by inducing bias and repetitive responding. It is concluded that (1) contrary to some recent reports, visual attention is disrupted, not improved, by peripherally injected AVP, (2) these effects reflect pressor potency, (3) the disruption induced by AMP reflects response alterations, while the peptide probably affects more cognitive mechanisms, and (4) certain recently described indices are more sensitive than others in detecting response bias.

Animals↗
PubMed1988

Prevalence of depression in general practice patients over 75 years of age.

The prevalence of depression among 74 male and 211 female patients aged 75 years or over registered with a group general practice was assessed, using the geriatric depression scale. Test scores of 0- 10, suggesting no depressive illness, were observed in 63 (85%) men and 172 (82%) women. Mild depression (scores 11-20) was observed in 10 (14%) men and 36(17%) women and severe depression (scores 21-30) in one (1%) man and three (1%) women. No significant statistical association was found with age or sex, suggesting that elderly men and women are equally prone to depression.A general practitioner found clinical manifestations of depression in 29 of the patients (10%). The geriatric depression scale scores were compared with clinical diagnoses of depression. Those with high scores were more likely to be depressed and vice versa. Thirty two elderly patients (11%) with no clinical manifestation of depression recorded high scores on the geriatric depression scale. These patients may be described as ;psychiatric cases'. Uncertainty about the importance of early identification of these cases necessitates further screening and regular follow-up of elderly patients.

Aged↗
PubMed1987

Contrasting effects of vasopressin, desglycinamide-vasopressin and amphetamine on a delayed matching to position task in rats.

The effects of peripherally injected arginine vasopressin (AVP: 0-25 micrograms/kg), its desglycinamide analogue (DGAVP: 0-25 micrograms/kg), which is practically devoid of pressor activity, and d-amphetamine (AMP: 0-1.25 mg/kg) were studied using a delayed (0-32 s) matching to position task (Dunnett 1985). A limited hold for responding (20 s) was in operation. This task enables an accurate assessment of forgetting in rats. AVP reliably improved per cent correct performance, and this effect was substantiated by accuracy indices derived from signal detection theory (TSD). DGAVP, however, was inactive, suggesting that the parent peptide's pressor properties were responsible for its beneficial effects. AMP disrupted performance in a dose-related manner, and was the only substance to alter a TSD bias index (responsivity index, RI), indicating a degree of response repetition at the highest dose. These results are consistent with some earlier reports, and suggest that AVP may enhance memory by peripheral action, while AMP disrupts performance. Closer inspection of the data, however, suggested that the peptide reduced general responsiveness. A new index to measure bias (Sahgal 1987) suggested that AVP-treated subjects restricted their sample, and choice responses to one side of the operant chamber, thereby achieving a spuriously high detection rate with few errors of commission (incorrect responses). It is concluded that AVP does not, after all, improve performance: on the contrary it has detrimental effects, and produce errors of omission (failure to respond).

Animals↗
PubMed1986

Desamino-D-arg8-vasopressin (DDAVP), unlike ethanol, has no effect on a boring visual vigilance task in humans.

It has been suggested that vasopressin (VP) and its analogues such as desamino-D-arg8-vasopressin (DDAVP) affect cognitive (including mnemonic) and attentional processes in man. We describe the effects of DDAVP and ethanol (EtOH) on young, healthy human volunteers, using a recently developed visual search task which assesses attention and vigilance. Over a 1-h session, the subject has to detect the occurrence of certain digits in a long list of random characters. A low dose of EtOH (0.33 ml/kg) tended to improve, and a higher dose (1.0 ml/kg) disrupted performance. DDAVP (20 or 60 micrograms/subject) had no effect whatsoever. It is concluded that intranasal administration of the peptide analogue does not markedly affect attention performance in human subjects.

Anxiety↗