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 beta-amyloid peptide-(25-35) fragment, but not beta-amyloid peptide-(1-28), shares with beta-amyloid protein-(1-42) the ability to self-aggregate and to induce neurotoxicity in vitro. This study examined the induction of amnesia in rats given intracerebroventricularly soluble or aggregated beta-amyloid peptide-(25-35) (5-45 nmol), or beta-amyloid peptide-(1-28) (15 nmol). Memory deficit in the water-maze test, examined 14 days after aggregated beta-amyloid peptide-(25-35) injection, was more pronounced than with soluble beta-amyloid peptide-(25-35). beta-Amyloid peptide-(1-28) only affected retention. These results confirm the direct amnesic properties of beta-amyloid peptides in the rat brain and showed that prior peptide aggregation markedly facilitates the appearance of amnesia.
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PMID:In vitro aggregation facilities beta-amyloid peptide-(25-35)-induced amnesia in the rat. 903 Aug 90

We characterized alterations in the ability of concussive brain injury (CBI) models to perform a water-finding task and examined effects of (+)-eburnamenine-14-carboxylic acid (2-nitroxyethyl) ester (VA-045), a novel apovincaminic acid derivative, on post-traumatic impairments in latent learning and memory processes. Two types of CBI-induced amnesia (retrograde and anterograde) were produced by means of post- or preacquisition head impact using a simple weight-drop device. Profound impairments of latent learning and memory processes related to retention and retrieval were observed in the CBI mice. In the CBI-induced retrograde amnesia model, VA-045 (0.5-4.0 mg/kg) significantly ameliorated impairments of latent learning and retention in both the retention test and the retest. In the CBI-induced anterograde amnesia model, the protective effects of the compound on impairments in latent learning and retention or retrieval were significant in both the retention test and the retest. These results suggested that VA-045 may be a novel cognitive enhancer for attenuating or protecting against the learning and memory dysfunction associated with CBI.
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PMID:(+)-Eburnamenine-14-carboxylic acid (2-nitroxyethyl) ester (VA-045), a putative cognitive enhancer, facilitates recovery from concussive brain injury-induced learning and memory impairments in mice. 906 83

The present experiment sought to determine in rats if 1) tolerance develops to the amnesic effect of diazepam after chronic treatment, 2) the sedative and amnesic effects of diazepam can be dissociated via differential rates of tolerance development, and 3) withdrawal from long-term diazepam treatment affects mnemonic processes. Rats were given diazepam (3 mg/kg) acutely or chronically for 5, 15, or 30 d prior to behavioral testing. Sedation was assessed as exploratory activity in an open field and amnesia was assessed as spatial learning in the Morris water maze. Tolerance to the sedative effect of diazepam was exhibited after 5 d pretreatment whereas tolerance to the amnesic effect of diazepam was exhibited only after 30 d pretreatment. Withdrawal from diazepam produced a transitory and mild disruption of spatial learning. The data demonstrate 1) tolerance can develop to the amnesic effect of diazepam with extended treatment, 2) the sedative and amnesic effects of diazepam are largely independent, and 3) withdrawal from chronic diazepam treatment can retard optimal learning.
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PMID:Tolerance develops to the spatial learning deficit produced by diazepam in rats. 907 73

1. No specific regimen has been developed to treat post-traumatic amnesia in man. In the present study, we examined the effects of (+)-eburnamenine-14-carboxylic acid (2-nitroxyethyl) ester (VA-045), a novel derivative of apovincaminic acid, on learning and memory deficits associated with a mild traumatic brain injury (TBI) in mice. 2. Two kinds of amnesia, TBI-induced retrograde amnesia (TRA) and anterograde amnesia (TAA), were produced by means of post- and pre-acquisition head injury, respectively, by a simple weight-drop device. A novel procedure of water-finding task was used to assess learning and memory functions. 3. Both TRA and TAA mice were dramatically impaired in the task performance, with prolonged latencies for finding and drinking in either retention test or retest, indicating that retention was impaired in TRA mice while learning and retention were impaired in TAA mice. 4. VA-045 administered 30 min post-trauma in TRA mice dramatically shortened the prolonged latencies for finding and drinking in both retention test and retest, indicating that VA-045 significantly improved the retention deficit observed in TRA mice. 5. VA-045 administered 30 min post-trauma in TAA mice dramatically attenuated the prolonged latencies for finding and drinking in both retention test and retest, indicating that VA-045 significantly improved the learning and retention deficits observed in TAA mice. 6. Administration of VA-045 30 min pre-trauma in normal mice markedly attenuated the delay of latencies for finding and drinking after trauma in both retention test and retest, which shows that VA-045 significantly prevented learning and retention deficits after TBI. 7. Motor activities were not significantly affected by either the TBI or the chemical treatment at the time of task examination in either experimental model. 8. It is concluded that VA-045 may have potential effects on learning and memory deficits observed in either TBI-induced retrograde or anterograde amnesia.
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PMID:Effects of VA-045 on learning and memory deficits in traumatic brain injury (TBI)-induced retrograde and anterograde amnesic mice. 931 33

Memory deficits frequently occur after taking benzodiazepines and ethanol. We studied in vivo hippocampal presynaptic glutamate transmission in conjunction with memory deficits induced by benzodiazepines and ethanol in rats as an animal model of amnesia. These drugs potently impaired spatial memory formation as evaluated by the Morris water maze task, the rank order among tested treatments being the combination of triazolam (20 micrograms/kg) with ethanol (2 g/kg) > or = triazolam (100 micrograms/kg) > ethanol (2 g/kg) > or = triazolam (20 micrograms/kg) > rilmazafone (20 micrograms/kg). On the other hand, these drug treatments also reduced glutamate release in the dorsal hippocampus but not in the cerebellum measured by microdialysis: the combined administration of triazolam with ethanol potently inhibited glutamate release to 60% of basal output in the dorsal hippocampus. These decreases in hippocampal glutamate transmission closely correlated with the extent of impairment of spatial memory performance (r = 0.990). Thus, the present results strongly indicated that presynaptic dysfunction in dorsal hippocampal glutamatergic neurons would be critical for spatial memory deficits induced by benzodiazepines and ethanol.
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PMID:Reduced dorsal hippocampal glutamate release significantly correlates with the spatial memory deficits produced by benzodiazepines and ethanol. 948 54

RGH-2716 is a novel 1-oxa-3,8-diazaspiro[4.5] decan 2-one, which was published to have potent inhibitory effect on neuronal Na and Ca movement and stimulatory action on nerve growth factor (NGF)-production, as well as to show significant antiamnesic activity in experimental amnesia models. The aim of the present experiments was to study the effect of the compound on the learning process and on the different stages of memory using water-labyrinth in normal and memory impaired young animals, as well as to study cognitive effect of RGH-2716 on aged animals. At the doses of 0.5 mg/kg i.p. or 3 mg/kg p.o. given before daily swimming, this compound improved the learning process of young animals impaired by either diazepam (DIA) or scopolamine (SCOP). In retrograde amnesia model RGH-2716 (3 mg/kg p.o.) significantly ameliorated consolidation process and retrieval of information impaired by SCOP or DIA. Nimodipine and vinpocetine (10 mg/kg p.o.) showed moderate effect compared to RGH-2716. Aged rats pretreated with daily i.p. RGH-2716 performed the tasks with significantly fewer errors and shorter swimming time than untreated aged rats. When aged animals had to solve a new labyrinth problem, treated aged rats showed significantly better learning ability than aged controls. One month of oral treatment of aged rats with 3 mg/kg dose of RGH-2716 two times daily resulted in a "tendency-like" improvement in learning of aged Fischer 344 and spontaneously hypertensive (SH) rats. The present results make RGH-2716 an interesting compound for the treatment of cognitive disorders.
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PMID:Effect of RGH-2716 on learning and memory deficits of young and aged rats in water-labyrinth. 957 Jul 17

Although protein synthesis inhibition has been shown to affect long-term memory in a wide variety of animal species, cases have been reported in which protein synthesis inhibition failed to affect memory consolidation [S. Wittstock, R. Menzel, Color learning and memory in honey bees are not affected by protein synthesis inhibition, Behav. Neural Biol., 62 (1994) 224-229.]. Most findings argue that the critical time for protein synthesis is during or immediately after training. However, other reports show a second time window, hours after training, where protein synthesis inhibition can cause amnesia [F.M. Freeman, S.P.R. Rose, A.B. Scholey, Two time windows of anisomycin-induced amnesia for passive avoidance training in the day-old chick, Neurobiol. Learn. Mem., 63 (1995) 291-295.][G. Grecksch, H. Matthies, Two sensitive periods for the amnesic effect of anisomycin, Pharmacol. Biochem. Behav., 12 (1980) 663-665.]. In this study, we addressed two questions: (1) Is protein synthesis essential for spatial memory? and (2) At what injection time window(s) will protein synthesis inhibition cause spatial memory amnesia? We report that bilateral intraventricular microinjection of anisomycin (Ani) impairs consolidation of long-term memory, in the hippocampal-dependent Morris water maze spatial memory task. Memory was impaired in a dose-dependent manner without affecting short-term memory. Spatial memory was affected only if Ani was injected 20 min before performing the task and not in any other time window before or after the behavioral test. The inhibition did not affect pre-existing memories or the capability to memorize once the effect of the inhibition diminished.
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PMID:Lateral ventricle injection of the protein synthesis inhibitor anisomycin impairs long-term memory in a spatial memory task. 960 54

The effects of single and repeated administrations of ipidacrine (NIK-247, 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride monohydrate) on scopolamine-induced spatial learning deficit were investigated in rats using the Morris water maze task. A single oral administration of ipidacrine (0.3 and 1 mg/kg) reduced the increased total latency induced by scopolamine in this task. The repeated administration of ipidacrine (1 mg/kg) of once a day for 5 successive days reduced the increased total latency induced by scopolamine to the levels of the saline-treated control rats in this task. In this pharmaco-kinetic study, ipidacrine was rapidly taken up into the brain within 5 min. Moreover, higher drug levels were observed mainly in the cortex and hippocampus, which both play important roles in learning and memory. Thus, a previous study together with this investigation indicate that ipidacrine improves amnesia which consists of the impairment of the working and reference memory in various animal models, suggesting that ipidacrine is a useful candidate for the therapy of patients with Alzheimer's disease.
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PMID:Ipidacrine (NIK-247), a novel antidementia, rapidly enters the brain and improves scopolamine-induced amnesia in rats during the Morris water maze task. 965 30

Neurosteroids have been reported to modulate learning and memory processes in aged animals and in pharmacological models of amnesia. We report here the effects of dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate (PREGS), and progesterone (PROG) on the learning impairment induced in mice by the muscarinic acetylcholine receptor antagonist, scopolamine. Spatial working memory was examined using the spontaneous alternation behavior in a Y-maze and long-term memory using place learning in a rectangular water-maze adapted for mice. Both DHEAS and PREGS (5-20 mg/kg, s.c.) prevented dose-dependently and significantly the scopolamine (2 mg/kg, s.c.)-induced alternation deficits. PROG (2-20 mg/kg, s.c.) failed to affect the scopolamine-induced deficits, but blocked, at 20 mg/kg, the beneficial effects induced by DHEAS or PREGS. In the water-maze, DHEAS (20 mg/kg) attenuated significantly the scopolamine-induced deficits, as observed during the acquisition sessions or the retention test. PROG (2, 20 mg/kg) did not affect the control or scopolamine-treated group performances, but blocked the ameliorating effect of DHEAS. Furthermore, in both tests, the selective sigma1 (sigma1) receptor antagonist NE-100 (1 mg/kg, i.p.) failed to affect the behaviors showed by the control or scopolamine-treated groups, but it blocked the ameliorating effects induced by DHEAS or PREGS. These results confirm the modulating role of neurosteroids in learning and memory processes and demonstrate that their modulation of the cholinergic systems involves an interaction with sigma1 receptors.
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PMID:The modulation by neurosteroids of the scopolamine-induced learning impairment in mice involves an interaction with sigma1 (sigma1) receptors. 966 79

These experiments explored the effects of glutamate, N-methyl-D-aspartate (NMDA) receptor blockade on the formation, retention, and expression of conditioned taste aversion (CTA) in young rats. Previous data from our laboratory suggested that ketamine administration potentiates a CTA in E18 rat fetuses. The current studies investigated this phenomenon in neonates. High-pressure liquid chromatography (HPLC) methods were used to determine the amount of ketamine that must be injected intraperitoneally (i.p.) to achieve brain ketamine levels in neonates comparable to those found in the fetuses from our previous experiments. Then, on their day of birth, Sprague-Dawley rat pups received injections of either 0.1, 10, or 70 mg/kg of ketamine HCI, i.p. or a Sal control injection. One-half hour later, pups were injected orally with either Saccharin (Sac; 10 microL of 0.3%) or water followed by an injection of either lithium chloride (LiCl; 81 mg/kg) or Sal (i.p.). The CTA was evaluated in two different tests. Two weeks after conditioning, the dam was anesthetized and the frequency with which pups attached to Sac-painted nipples versus nipples painted with water was measured (i.e., the nipple taste test, NTT). Controls for state-dependent learning were run in which 10 mg/kg of ketamine or saline (Sal) was administered before both taste aversion conditioning and the NTT. After weaning, the CTA was also evaluated by measuring the amount of Sac (0.3%) or water consumed during a two-bottle test. Neonates that received Sal control injections before the Sac + LiCl pairing acquired CTAs and avoided Sac-painted nipples. However, the pups injected with ketamine on the conditioning day only (P0) did not avoid Sac-painted nipples (as compared to controls). Pups that had ketamine both at the time of CTA training and testing, or just before the NTT, also failed to avoid Sac-painted nipples. Ketamine's acute effects apparently influenced the outcome of the NTT of state-dependent control subjects. Rat pups that received the highest doses of ketamine (10 or 70 mg/kg) and tasted Sac on P0 later failed to show a neophobia for Sac-painted nipples. Whereas, rat pups that received the high dose of ketamine and water on P0, later exhibited a neophobic response. These data suggest that ketamine did not impair the animal's ability to taste Sac. These data reflecting a ketamine-induced blockade of neonatal CTAs may be contrasted with our previous findings in which ketamine potentiated fetal CTAs. However, they are in consonance with data from adult rats suggesting that ketamine can cause an amnesia for CTAs. NMDA receptor blockade may shape memory formation in a manner that is dependent on the stage of brain development.
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PMID:Ketamine blocks a conditioned taste aversion (CTA) in neonatal rats. 974 8


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