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Biomedical subjects

A Sahgal

Publications and source records attributed to A Sahgal.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effects of vasopressin, des-glycinamide vasopressin and amphetamine on a combined passive and active avoidance task.

The effects of peripherally injected arginine vasopressin (AVP), its des-glycinamide derivative (DGAVP), which has limited pressor activity, and d-amphetamine (AMP) were studied on a combined passive and active avoidance task (Carew 1970). In this procedure, the rat experiences mild foot-shock in one of two distinctively coloured compartments, followed by drug treatment. On the next day, re-entry latency into either of the two compartments is measured (latency index), and the actual compartment chosen is noted (choice index). Both measures were affected by the intensity of the shock. A moderate dose of AVP (25 micrograms/kg) increased latencies, but only when a relatively low shock intensity was used; choice was not markedly affected. DGAVP did not significantly affect performance under any condition. AMP affected latency scores as well as choice behaviour at the lower shock level but, presumably due to "ceiling" effects, did not exert an effect in the high shock condition. The negative DGAVP findings suggest that the behavioural potency of peripherally injected AVP was due to pressor activity, rather than any direct action on cognitive mechanisms. Moreover, this indirect AVP effect on mnemonic performance was relatively weak, since only the latency, but not choice, measure was significantly affected. It is concluded that the Carew paradigm provides a more comprehensive assessment of behaviour than traditional passive or active avoidance procedures.

Animals↗
PubMed1986

Histidyl-proline, a rapidly degraded metabolite of thyrotropin releasing hormone, has behavioural activity.

The effects of intracerebroventricular (ICV) administration of histidyl-proline (His-Pro; 0, 1, 10 and 100 micrograms/rat), a rapidly degraded metabolite of thyrotropin releasing hormone (TRH), were assessed using three behavioural paradigms. Locomotor activity was significantly increased over 30, but not 90, min following administration of the highest dose. This stimulatory effect was more apparent when naive rats were tested in an open field without any prior exposure to the apparatus; the effect was attenuated on a second exposure. His-Pro treated subjects also tended to prefer the area near the walls of the apparatus. The effects of the dipeptide on visual perception were studied, using a two-choice task. A low but not high (10, versus 100 micrograms/rat) dose of His-Pro increased response switching, but did not affect response repetition, latencies or percent correct performance. The results indicate that His-Pro can alter behaviour by affecting motor output, as well as emotional processes.

Animals↗
PubMed1986

Effects of peripherally injected pituitary peptides on recognition memory in pigeons.

The effects of peripheral injection of arginine vasopressin (AVP), oxytocin (OT), arginine vasotocin (AVT), adrenocorticotrophic hormone (ACTH4-10) and alpha-melanocyte-stimulating hormone (alpha-MSH) were studied, using pigeon subjects and a pair comparison task, with and without intervening delays between stimuli presentation. The highest dose (20 micrograms/kg) of AVT impaired performance by disrupting input, but not storage. General cognitive ability was unimpaired, as were perceptual mechanisms. None of the other peptides affected recognition memory, in that forgetting curves were unchanged when compared with control. The results are discussed in terms of species-specific roles for these peptides.

Adrenocorticotropic Hormone↗
PubMed1986

Evaluation of the mental function of the elderly in a general practice.

A mental function test was carried out on 378 individuals over 70 years of age registered with a group practice in the city of Newcastle upon Tyne. A high score (11 or over) was observed in 64.9% of women and 78.3% of men; a medium score (between three and 10) was observed in 34.0% of women and 20.8% of men; and only 0.8% of individuals of both sexes were found to have a low score (less than three). It was found that older age groups of both sexes had lower scores than younger groups (P < 0.001) and this was more pronounced in women than men (P < 0.05).These observations are significantly different (P < 0.001) from those obtained in hospital studies. The need for surveillance which influences mortality, morbidity and resource allocation is discussed.

Aged↗
PubMed1985

Abnormal behavioural changes associated with vasopressin-induced barrel rotations.

Arginine-8-vasopressin (AVP) was injected into the cerebral ventricles of rats in order to characterize the dose-response relations of the convulsant actions of AVP and to obtain a detailed description of other acute behavioural effects. The incidence of barrel rotations, a violent and apparently uncontrolled motor activity during which rats rotate about their long axis, was found to be dose dependent, with a threshold of between 1 and 10 ng per rat. Other behavioural effects of AVP including immobility, titubation, ataxia, backward walking, and inhibition of exploratory activities and of grooming were seen at doses as low as 100 pg. These behavioural effects occurred within 9 min after injection, and thus have the same time course as barrel rotations. These acute actions of AVP may be significant in interpreting the effects of AVP on cognitive processes and memory and should also be taken into consideration in the clinical use of AVP as an anti-amnestic.

Animals↗
PubMed1985

The effects of thyrotropin releasing hormone on rats with lesions of the mesolimbic and nigrostriatal dopamine systems.

We report the effects of intracerebroventricular (ICV) administration of thyrotropin releasing hormone (TRH), a TRH metabolite histidyl-proline diketopiperazine (DKP) and systemically administered d-amphetamine (AMP) on the locomotor activity of two groups of rats which had previously received bilateral injections of either 6-hydroxydopamine (6-OHDA) or saline into the nucleus accumbens. Both TRH and AMP enhanced locomotor activity in control, but not lesioned animals, whereas DKP had very little effect. In a second experiment, the effects of ICV administration of saline, TRH and DKP were tested on rotational behaviour in rats with unilateral lesions of the substantia nigra. Neither peptide induced significant circling on its own. However, coadministration of TRH or DKP with systemically administered AMP enhanced rotation above that found after injection of AMP alone. These results suggest that TRH can act on mesolimbic and nigrostriatal dopamine systems, either directly or by modulating the effects of other dopaminergic agents.

Animals↗
PubMed1985

Drug effects on memory: assessment of a combined active and passive avoidance task.

We evaluate a little-known avoidance task first described by Carew, which enables the simultaneous assessment of two indices relevant to the study of memory processes, passive avoidance re-entry latency, and active avoidance choice. As an illustration, the effects of 0, 1 and 10 mg/kg amphetamine, peripherally injected immediately following the learning trial, were studied using two different shock intensity conditions (mild and moderate). The latency measure indicated that the drug improved consolidation, but the choice measure suggested that this enhancement was at best marginal; shock intensity was found to be a critical factor. It is concluded that this unique task is superior to some traditional avoidance techniques used in assessing memory.

Amphetamine↗
PubMed1984

Choice, as opposed to latency, measures in avoidance suggest that vasopressin and oxytocin do not affect memory in rats.

Latency measures from passive avoidance studies are frequently used as an index of memory. Thus, vasopressin (VP) is thought to enhance memory, since it has been shown to increase re-entry latencies. Conversely, several substances, such as oxytocin (OT), are supposed to have amnestic effects since they may decrease latencies. We describe a novel avoidance design, which allows latency to be assessed, but also permits the animal to re-enter into a distinctive compartment where shock had not been experienced (choice measure). Latency scores indicated that VP may improve memory, but the choice index suggested that this was not the case.

Animals↗
PubMed1984

N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) affects locomotor activity without producing a nigrostriatal lesion in the rat.

Drug addicts abusing heroin substitutes contaminated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and perhaps those who work with this substance, may develop symptoms similar to those seen in Parkinson's disease [7, 12, 13]. We describe the results of a study in which rats were given daily injections of MPTP for two weeks. A progressive suppression of activity was seen, but the subjects rapidly recovered when treatment ceased. The animals were then injected with D-amphetamine or apomorphine; the former drug enhanced activity, to levels seen in control (non-MPTP treated) subjects. Apomorphine had no effect, either on control or MPTP-treated subjects. The effects of acute (0, 2.5, 5.0 and 10.0 mg per rat) administration of MPTP were also studied. The two lower doses significantly decreased activity, but the highest dose did not. Histological examination showed that 2 weeks' treatment with MPTP did not produce neuronal degeneration in the pars compacta of the substantia nigra (SN). In these animals, there were no changes in levels of dopamine, 5-hydroxytryptamine, or their metabolites in either the SN or the caudate nucleus. MPTP had no effect on the levels of neurotensin, somatostatin and substance P in several brain areas. It is concluded that MPTP has reliable effects on locomotor activity in rats without producing measurable histological or neurochemical changes in the nigrostriatal dopaminergic system.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

A critique of the vasopressin-memory hypothesis.

During the past 20 years, evidence has accumulated to suggest that the neuropeptide vasopressin (VP) enhances memory by acting on central mechanisms, and that oxytocin (OT) has amnestic effects. In this review, the evidence for the memory hypothesis with respect to VP is considered and alternative interpretations evaluated. A critical approach has been adopted; negative findings, design considerations and problems with the various hypotheses are given prominence. It is concluded that the memory hypothesis fails to provide an adequate account, and some alternative theories and suggestions are discussed. It is speculated that the peptide may affect behaviour by two distinct mechanisms: peripheral action may involve reinforcement mechanisms, but its central role may be to modulate arousal level, especially in stressful situations.

Arginine Vasopressin↗
PubMed1984

Hippocampal lesions disrupt recognition memory in pigeons.

Pigeons given bilateral hippocampal lesions, together with sham-operated and normal birds, were trained on a Konorski pair comparison (recognition memory) task. In this paradigm, the subject must indicate whether or not two successively presented stimuli were identical, or dissimilar; a delay may be interposed between the presentations. All subjects learned the basic (simultaneous, or no delay pair comparison) task to similar levels of performance, indicating that neither perceptual nor general cognitive abilities were selectively impaired. However, the hippocampal group was impaired when delays were interposed, i.e. when (labile) memory was required. These subjects tolerated only short delays, and lost information('forgot') at faster rates. A second experiment explored (a) the importance of acquisitional variables by limiting exposure to the to-be-remembered stimulus (S1), and (b) the role of proactive interference, by varying the inter-trial-interval (ITI). Neither manipulation selectively disrupted the hippocampal group, although reductions in S1 and ITI duration progressively impaired performance in all groups. It is concluded that the avian and mammalian hippocampii are functionally similar, at least with respect to recognition memory processing. The results are discussed in terms of the hypothesis proposed by Olton et al., that hippocampal lesions impair working, but not reference, memory probably by disrupting a process analogous to storage.

Animals↗
PubMed1984

Adrenocorticotrophic hormone and melanocyte stimulating hormone do not affect performance in hippocampus-lesioned or control pigeons.

Pigeons, given bilateral lesions of the hippocampus, as well as unoperated control subjects, were trained on an operant task in which they had to peck a left hand key if both members of a successively presented stimulus pair were the same, and a right hand key if they were different. During extensive training, the 'same' pairs (green-green or red-red) were presented at twice the frequency of the 'different' pairs (green-red or red-green), thus biasing responding to the left hand key. The effects of intramuscular (i.m.) injections (0, 10 and 100 micrograms/kg) of an active fragment of adrenocorticotrophic hormone (ACTH4-10) and alpha-melanocyte stimulating hormone (MSH) were then studied. On any given test (peptide or saline) day, all stimulus pairs were presented with equal frequency. Although the control birds' performance was consistently better than the lesioned birds, neither ACTH4-10 nor MSH affected performance under any conditions. It is concluded that peripheral injection of these peptides has little, if any, effect on cognitive behaviour in birds.

Adrenocorticotropic Hormone↗
PubMed1984

The effects of thyrotropin releasing hormone on a visual discrimination task in rats.

The effects of intracerebroventricular (ICV) administration of thyrotropin releasing hormone (TRH, 1 and 50 micrograms) were assessed on a two-choice visual discrimination task. The data were analysed using signal detection theory techniques in order to test for changes in cognitive and response factors. No significant changes in performance were observed. In a second experiment, the effects of TRH (100 micrograms ICV) on performance were compared with amphetamine (AMP, 1 mg/kg, intra-peritoneally, IP) and a metabolite of TRH, histidyl-proline diketopiperazine (DKP, 100 micrograms ICV). No significant effects on performance as measured by standard indices were observed. However, both TRH and AMP, but not DKP, significantly increased perseverative responding on one lever with respect to saline. In keeping with recent evidence, it is concluded that the traditional non-parametric signal detection parameters of sensitivity and bias are insensitive to certain strategies. Possible mechanisms for the perseveration of responding, and its relationship to stereotypic behaviour, are discussed in the light of the known effects of each compound on dopaminergic systems.

Adenosine Monophosphate↗
PubMed1983

Corticotrophin releasing factor is more potent than some corticotrophin-related peptides in affecting passive avoidance behaviour in rats.

The peptides corticotrophin releasing factor (CRF), ACTH4-10 and alpha-MSH have previously been shown to be behaviourally and neurochemically active. Using a passive avoidance task, we studied the effects of intra-ventricular administration of these peptides (0, 10 or 100 ng/rat) given either immediately following the learning trial, or 1 h prior to retention (24 h post-learning) test. We found that they affected behaviour; in some cases improving and in others disrupting performance. Statistical examination of the data suggests that these substances probably act on arousal mechanisms, in a manner reminiscent of the effects of vasopressin [13, 15].

Adrenocorticotropic Hormone↗
PubMed1983

A comparison of the effects of vasopressin and oxytocin with amphetamine and chlordiazepoxide on passive avoidance behaviour in rats.

On the basis of results obtained from passive avoidance studies, we have argued that the neuropeptide vasopressin could act on arousal, rather than memory processes in rats (Sahgal et al. 1982). In this report, we examine the effects of substances that are known to increase (d-amphetamine) or decrease (chlordiazepoxide) behavioural arousal, and compare the data with those obtained after vasopressin or oxytocin treatment. All four substances yielded broadly similar bimodal results (although the oxytocin data failed to reach significance). We argue for an arousal interpretation which suggests that performance and arousal are related in an "inverted-U" manner. The data also indicate that care must be taken in selecting appropriate statistical tests.

Animals↗
PubMed1983

The effects of vasopressin on positively rewarded responding and on locomotor activity in rats.

It has been suggested that arginine-vasopressin (AVP) enhances cognitive, and especially mnemonic, ability. Most studies have employed shock avoidance paradigms; we report the results of a study in which saline or vasopressin (0, 0.5 or 1 microgram, mcg, per rat, subcutaneous) pre-treated rats learned to press a lever for food reward. AVP was found to have a disruptive effect on aquisition, particularly when the tendency for these rats to produce extreme learning scores was taken into account. Locomotor activity, with and without vasopressin pre-treatment (0, 0.5, 1 or 2 mcg/rat), was also studied. Only the highest dose significantly reduced activity; therefore, the effects of AVP on acquisition are unlikely to have been caused by motor disruption. The results are discussed in terms of an hypothesis which suggests that AVP enhances arousal, hence influencing performance.

Animals↗