Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002622 (amnesia)
 5,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of peptides derived from ACTH on the formation of long-term memory have been investigated in male mice. Post-training administration of ACTH 4-10-L-Phe-7 (ACTH-L) improved retention for both passive and active avoidance tasks. Administration of ACTH 4-10-D-Phe-7 (ACTH-D) impaired retention for both tasks. The optimum dose for ACTH-L was about 0.3 mg/kg; the optimum dose for ACTH-D was in the range of 1.0-3.0 mg/kg. Using the passive avoidance task, it was shown that either drug had to be administered within 60 min of training to be highly effective. Amnesia produced by anisomycin (Ani), an inhibitor of protein synthesis, was lessened by ACTH-L and increased by ACTH-D, ACTH-D opposed the memory facilitating effects of ACTH-L. Using intact mice, ACTH-L or ACTH-D did not significantly change the incorporation of valine into protein, nor did these peptides influence the inhibition of protein synthesis caused by anisomycin. The results show that ACTH may play a major role in memory processing, perhaps by facilitating essential protein synthesis at sites specific for the memory being established.
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PMID:Effects of ACTH peptide fragments on memory formation. 18 31

The ACTH 4-9 analog, H-Met((O2)-Glu-His-Ph-D-Lys-Phe-OH (Or 2766), attenuates in rats CO2-induced amnesia for a one-trial passive avoidance step-through response when administered prior to the retrieval test but not when given prior to acquisition. Even a dose of 0.001 mug/rat Org 2766 yields an anti-amnesic effect. In this respect Org 2766 is more active than the ACTH fragment ACTH 4-10. An anti-amnesic effect was also obtained when Org 2766 was administered orally. ACTH 4-10 (100 mug/rat) has to be given SC within 8 hr of the retrieval test in order to be effective. A similar time span of effectiveness was observed when Org 2766 was SC injected in a dose of 0.1 mug/rat. The anti-amnesic effect of ACTH 4-10 remains when the time interval between acquisition and retrieval is extended beyond the usual 24 hr. The same appeared to be true for SC ADMINISTERED Org 2766. It is suggested that ACTH-like peptides, and particularly the orally active Org 2766, may be helpful in the treatment of deficient mental performance.
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PMID:Reversal of amnesia by an orally active ACTH 4-9 analog (Org 2766). 18 32

Two antibiotic inhibitors of protein synthesis, emetine and pactamycin, have been tested for their effects on cerebral and peripheral protein synthesis and amnesia. Peripherally administered emetine but not pactamycin inhibited cerebral protein synthesis, although this inhibition was lower than that observed with cycloheximide or anisomycin. Pactamycin had a lesser effect on adrenal protein synthesis than emetine. This was reflected in the ability of emetine but not pactamycin to block ACTH-induced corticosteroidogenesis. Anisomycin and cycloheximide caused amnesia in a passive avoidance task, whereas pactamycin and emetine did not. These results are inconsistent with the amnesia being due to inhibition of protein synthesis in a peripheral organ. They are also inconsistent with the amnesia being due to the suppression of an adrenocortical response as previously suggested. No obvious correlation between amnesia and the mechanism of protein synthesis was observed. The most parsimonious explanation is that inhibition of cerebral protein synthesis is necessary for amnesia.
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PMID:Protein synthesis and amnesia: studies with emetine and pactamycin. 19 50

Application of footshock during the acquisition trial of a one-trial passive avoidance test is associated with a rise in the concentration of serotonin in the hippocampi of rats 24 hr after termination of the acquisition trial. Rats subjected to amnesic treatment with carbon dioxide (CO2) immediately after footshock do not show this rise in the hippocampal concentration of serotonin. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 (7D-Phe), alleviate CO2-induced amnesia for the passive avoidance response when administered 1 hr before retrieval test 24 hr after acquisition. These peptides do not have anti-amnesic activity when given before acquistion. Another ACTH-analogue, ACTH 11-24 does not affect amnesia, given before either the acquisition or the retrieval test. The anti-amnesic effect of ACTH 4-10 AND ACTH 4-10 (7D-Phe), was correlated with a rise in the hippocampal serotonin concentration similar to that observed in non-amnesic animals. Pre-acquisition treatment with ACTH 4-10 or administration of ACTH 11-24 did not affect hippocampal serotonin concentrations. Changes in the hippocampal concentrations of noradrenaline, dopamine, tryptophan and tyrosine were not related to the behavioural activity of any of the peptides. It is suggested that alterations in hippocampal serotonin metabolism 24 hr after acquisition of a passive avoidance response are associated with the retrieveability of the passive avoidance response.
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PMID:Parallel changes in behaviour and hippocampal monoamine metabolism in rats after administration of ACTH-analogues. 20 81

Pituitary hormones profoundly influence behavior through direct actions on the brain. One of these behavioral effects is the attenuation of experimental amnesia. Traditionally, amnesia is considered as a "loss of memory." Memory comprises at least 2 stages: input (memory consolidation) and output (memory retrieval). Theoretically, disturbance of either aspect of memory may be the cause of amnesia. Also, it is possible that amnesia is based on a factor or factors not related to memory. Data and theories on amnesia in man were reviewed. Some salient features were mentioned: (1) amnesia can be induced by a variety of agents; (2) amnesia covers periods ranging from seconds to years; (3) amnesia gradients can be established; (4) amnesia is to a large extent reversible. From this survey, it seems possible that amnesia is not a homogeneous phenomenon and that even in one person a disturbance of both memory consolidation and memory retrieval may be produced by one and the same event. Animal studies in general have confirmed these conclusions. We have developed an animal model in order to study the effects of pituitary peptides on amnesia. This model is based on CO2-induced amnesia for a one-trial passive avoidance response in rats. This amnesia could be attenuated by treatment with ACTH-analogs 1 hour before the retrieval test. This anti-amnesic effect of ACTH-analogs was not dependent on the nature of the behavioral response or the amnesic treatment. The vasopressin-analog DGLVP similarly exerted an anti-amnesic effect when injected before the retrieval trial. In contrast to ACTH-analogs, however, it also reduced the amnesia when injected before acquisition. These results suggest that amnesia may comprise a "faulty-consolidation" and a "faulty-retrieval" component, which may be amended by different pituitary hormones. The study of the anti-amnesic activity of peptides therefore not only serves to characterize the nature of the behavioral effect of these peptides but may also prove to be helpful of the unraveling of processes involved in amnesia.
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PMID:Pituitary hormones and amnesia. 21 89

ACTH affects behavior of rats. The results of the reported experiments suggest that ACTH effects on conditioned behavior are the result of an improved motivation or attention. The ACTH fragments, ACTH 4--10 and ACTH 4--9, have the behavioral effects of ACTH but are devoid of endocrine activities. The ACTH 4--9 analog H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH (Org 2766) has behavioral activity after oral administration. ACTH-like-peptides restore the behavioral deficiencies of hypophysectomised rats and delay extinction of conditioned behavior of normal rats independent of the type of conditioning. So is extinction of pole jump avoidance and extinction of conditioned tast aversion delayed after Org 2766. Moreover ACTH-like peptides reduce the behavioral deficit in rats with amnesia even when the treatment is given two weeks after the induction of amnesia. In man the administration of a single dose of ACTH 4--10 on Org 2766 reduces the duration of lapses as well as the number of errors of volunteers in a continuous performance task. These and similar observations suggest that ACTH-like peptides may be of practical consequence for the therapy of patients with impairments of cognitive processes.
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PMID:[Possible consequence of ACTH-like peptides for human mental performance (author's transl)]. 22 80

The hormonally induced stresses have been studied for their effect on higher nervous activity (HNA) of rats under conditions of low-(1760 m above the sea level) and highland (3200 m above the sea level). Hydrocortisone-induced stress (HIS) in mountains decreases to an optimal degree the latent period (LP) of conditioned reflex of active avoidance (CRAA) and strengthens differentiating inhibition (DI). In mountains and on plain it impedes appearance of extinctive inhibition (EI). DOCA-induced stress (DIS) has the same effect though in the emergency period of adaptation it sharply (unlike GIS) increases the number of cases of CRAA amnesia manifestation and prolongs their LP. ACTH-induced stress (AIS) makes the appearance of amnesia cases more frequent and prolongs LP of realized CRAA, unlike DIS, over all the periods of Alpine adaptation. However, DI strengthens, while EI is hindered irrespective of the altitude level. Injection stress in mountains occurs with deviations of HNA; the number of cases of the CRAA amnesia increases as well as differentiation disinhibition. DI fails rapidly being tested for strength. Adaptation of intact rats to highland occurs faithfully without essential changes of LP but with impeded development of EI.
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PMID:[Effect of hormone-induced stress and high altitude on the higher nervous activity of rats]. 165 80

Rats were submitted to a normal (25% casein) or a low protein diet (8% casein) from the day of birth until the age of 110 to 120 days. Hypothalamic beta-endorphin-like immunoreactivity was lower in the animals raised and maintained with the low protein diet, and, in addition, it did not respond to training in a step-down inhibitory avoidance task with or without footshock with a depletion, as was the case with the normal diet animals. In the animals submitted to the normal protein diet posttraining ACTH (0.2 micrograms/kg) and beta-endorphin (1.0 micrograms/kg) caused retrograde amnesia of a step-down inhibitory avoidance task, and pretest administration of these substances had no effect of its own, but was able to reverse the amnesia induced by their previous posttraining administration. In the animals submitted to the low protein diet, results were similar except that pretest beta-endorphin caused amnesia on its own. On the basis of previous findings which suggest that pretest actions of ACTH and beta-endorphin depend on their endogenous release at the time of training, the present results are compatible with a malfunction of the brain beta-endorphin system in the undernourished animals.
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PMID:Effect of posttraining and pretest beta-endorphin and ACTH administration in normal and protein malnourished rats. 256 Jan 73

Rats received an ip injection of 0.2 microgram/kg of ACTH-(1-39) 1 min after step-down inhibitory avoidance training and/or 5 min prior to retention testing. Experiments were carried out either in the morning or in the afternoon using either a 3- or a 24-h training-test interval. Post-training ACTH induced memory facilitation in the morning and amnesia in the afternoon at both training-test intervals. Pretest ACTH reversed the afternoon amnesic effect, also at both training-test intervals. In addition, pretest ACTH induced a naloxone-reversible memory enhancement, both on its own and in animals treated with a facilitatory post-training dose of ACTH in the morning; this effect was seen only at the 24-h training-test interval. Naloxone had no effect of its own and did not influence the reversal of ACTH-induced amnesia caused by pretest ACTH in the afternoon. The results point to the variety of memory modulatory influences of ACTH, and to some of the factors involved in the elicitation of one or other effect, namely, the presumable basal rate of secretion of endogenous ACTH, and the previous pharmacological history of the animal.
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PMID:Post-training and pretest effects of adrenocorticotropin on retention: the influence of the hour of the day, the training-test interval, and pretest naloxone administration. 284 20

On the basis of the idea of the important role of neurotransmitter systems in realization of neuropeptide effects, the participation was studied of the monoaminergic systems in the mechanisms of the ACTH analogue influence on the processes of learning and memory in control animals and animals with a changed functional state of the monoaminergic systems. In parallel the influence was studied of the ACTH analogue on the content of the endogenic monoamines in various brain structures of rats. It has been shown that administration of the ACTH analogue in a dose of 10 mcg affects the elaboration and preservation of conditioned reflexes (CRs) of passive avoidance, CRs of two-side avoidance and labyrinth CRs only in conditions of changed functional state of the monoaminergic systems. Amnesia, usually elicited by 5-oxytryptophane and disulfiram is prevented by administration of the ACTH analogue. Administration of the ACTH analogue is accompanied by the intensification of serotonine metabolism in the midbrain and medulla and by an increase of noradrenaline content in the hypothlamus.
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PMID:[Effect an ACTH analog on the processes of learning and memory in rats]. 285 41


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