Reversal of conditioned aversions in normal and micrencephalic rats.
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Animals↗
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Operant discrimination of an interoceptive stimulus in rhesus monkeys.
Five rhesus macaques monkeys surgically prepared with Thiry small intestinal (jejunum) loops and implanted brain electrodes were restrained in primate chairs and kept on 23-hr deprivation-feeding cycle. After being trained to press a lever for sugar pills on an FR 25 schedule of reinforcement, a discrimination training procedure was established. Lever presses were reinforced during the S(D)-a non-aversive mechanical stimulus applied to the internal walls of the Thiry loop by rhythmic inflation-deflation of a small latex balloon by air at the rate of one cycle per sec at 100 mm Hg pressure. The S(Delta) was the absence of the visceral stimulation. The monkeys successfully discriminated between presence and absence of the internal stimulus. A discrimination reversal was attempted and completed on one monkey. The results clearly show operant discrimination based on an interoceptive stimulus. Cortical and subcortical EEG records reflected the onset but not termination of the visceral stimulation.
Animals↗
Effects of two ACTH analogs on successive odor discrimination learning in rats.
Olfactory discrimination learning has been shown to provide a powerful tool to investigate the mechanisms involved in the formation, storage and retrieval of information in rodent CNS. In the present study we tested the effects of two ACTH analogs, which were previously reported to influence the processes of learning and memory, on various olfactory learning tasks. The ACTH(4-9) analog HOE 427 produced an apparent increase in storage of olfactory information as shown by the difficulty experienced by the animals to rapidly reverse their behavioral responses to previously learned odors. Similarly, the ACTH (4-9) analog ORG 2766 appears to enhance the storage of olfactory information when administered either before or after the learning trials. These data are consistent with the notion that ACTH and related analogs facilitate performance in a variety of learning tasks. In addition, our results suggest possible mechanisms by which some neuroactive peptides might modulate learning and memory processes in the CNS.
Adrenocorticotropic Hormone↗
Evidence of state dependent learning of brightness discrimination in hypothermic mice.
Shock-elicited escape behavior of C57Bl mice in a brightness discrimination task was examined to investigate the effects of hypothermia on acquisition and reversal. Neither acquisition nor reversal was impaired by 7 degrees C or 13 degrees C decreases in central body temperature when body temperature remained at those levels throughout testing. However, body temperature changes from acquisition to reversal were accompanied by memory deficits during reversal if acquisition occurred at body temperature decreased by 13 degrees and reversal occurred at normal body temperature or body temperature decreased by 7 degrees and reversal at body temperature decreased by 13 degrees. This finding suggests the occurrence of a state dependent discrimination response: an instance of asymmetrical dissociation. In addition, during acquisition, latency of the escape response was longer in hypothermic animals than in controls, and should be interpreted as a performance deficit, rather than failure or delayed rate of learning. Depressed intertrial activity also was observed in hypothermic animals.
Animals↗
The nature and processes of preverbal learning: implications from nine-month-old infants' discrimination problem solving.
Nine-month-old infants' performance on discrimination-learning problems was investigated in four experiments using the synchronous reinforcement paradigm. These experiments were organized around basic theoretical postulates concerning the relation between attention and learning. In each of the experiments, infants were trained to respond differentially to a particular stimulus feature, with the goal of establishing whether they could learn to respond to a particular stimulus feature under conditions where other stimulus dimensions were present and varying. In the first experiment, 48 infants were trained to fixate visually on a particular feature in a pair of stimuli that varied in color, form, and position dimensions. Contingencies for responding were then shifted either within a dimension (reversal shift) or across dimensions (nonreversal shift). Infants learned to respond to the reinforced feature during initial training; moreover, infants assigned to a reversal shift condition showed a higher level of transfer of learning during the test phase than those assigned to a nonreversal shift condition. The second experiment extended the results of Experiment 1 by testing 48 additional infants under conditions in which the number of varying irrelevant dimensions was increased during the shift phase. Although the difficulty added to this task by this manipulation made transfer more difficult for all infants, results again indicated that transfer of learning was more evident for infants in a reversal shift than a nonreversal shift condition. In the third experiment, 64 infants were trained in a similar manner, except that completely new values were substituted during shift phases on the color and form dimensions. This manipulation was meant to probe whether infants were formulating a dimension response from previous training and to test the predictions of such dimension processing for transfer of learning to a functionally new problem. Infants were reinforced for fixating on a new feature either within the same dimension as during training (intradimension shift) or within the dimension that was not originally trained (extradimension shift). Transfer of learning was clearly superior in the intradimension shift condition. The findings of the first three experiments suggested that, during discrimination-learning problems, infants selected and tested individual stimulus features and dimensions from an array of potential solutions to the problem until discovering the one that was consistently associated with reinforcement.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Photoperiodic control of antler cycles in deer. V. Reversed seasons.
Newborn and weanling fawns were held under reversed annual light cycles to learn if the subsequent replacement of their antlers would coincide with the anniversary of their births, as occurs in nature, or adapt to the artificial seasons of increasing day lengths even when these fall at the "wrong" time of year. The first sets of antlers developed at approximately the normal age when the deer were yearlings. These antlers, however, were shed and replaced half a year earlier than would otherwise have occurred under natural environmental conditions. It is concluded that the onset of renewed antler growth is not a response to every other time the photoperiod increases or decreases, but is triggered by lengthening days, irrespective of the age of the deer.
Age Factors↗
The effects of lesions in telencephalic visual areas of pigeons on dimensional shifting.
Two experiments on dimensional shifting in pigeons with lesions of telencephalic visual areas are reported. In the first, pigeons were initially trained on a pattern discrimination with color irrelevant and then the color discrimination was made relevant and pattern irrelevant. Pigeons with ectostriatal lesions made more errors than shams or Wulst-lesioned animals on the pattern problem, but there was no difference among the three groups on the shift to color. In the second experiment, the same discriminations were studied in the reverse order: the animals first learned the color problem and then shifted to pattern. In this case the ectostriatal-lesioned animals showed a deficit on both problems. The Wulst-lesioned animals, on the other hand, showed a deficit on the shift to pattern but not on the original color problem. The results are discussed in terms of the nature of the deficits caused by the two lesions and their meaning for questions of comparative neurobiology.
Animals↗
NS-3(CG3703), a TRH analog, ameliorates scopolamine-induced memory disruption in rats.
The effects of a metabolically stable TRH analog, N-[[(3R, 6R)-6-methyl-5-oxo-3-thiomorpholinyl]carbonyl]-L-histidyl-L- prolinamide tetrahydrate (NS-3, CG3703) on the scopolamine-induced memory disruption in maze performance tests were investigated in rats. a) In the delayed nonmatching-to-sample (DNMS) task using a T-maze, NS-3 (0.3 mg/kg) produced a significant reversal of the marginal disruption of choice accuracy induced by scopolamine (0.3 mg/kg) at the short (5 s) and long (120, 480 s) interval delays. Physostigmine (0.5 mg/kg) produced a significant reversal only at a 5-s interval delay. b) In the eight-arm radial maze task, NS-3 (0.3 mg/kg) significantly reversed the deficit of choice accuracy induced by scopolamine (0.3 mg/kg), whereas neither TRH (3-30 mg/kg) nor physostigmine (0.1-1 mg/kg) had any effect. The consistent reversal of these maze-learning performances by NS-3, but not by TRH or physostigmine, may be due to its potent enhancement of cholinergic and noradrenergic neuronal activities.
Animals↗
Inactivation of the interpositus nucleus blocks the conditioned response acquired by a somatosensory conditioned stimulus in rabbit eyeblink conditioning.
1. Earlier studies suggest that the memory trace for the conditioned eyeblink reflex is formed and maintained in the interpositus nucleus (IPN) in the deep cerebellar nuclei when either an auditory or visual stimulus is used as a conditioned stimulus (CS). 2. In the present study, the eyeblink reflex of the rabbit was conditioned to a somatosensory CS (an airpuff onto the back). 3. In well-trained animals, the IPN was reversibly inactivated by local cooling and the existence of the learned responses to the CS was then tested. 4. The reversible IPN inactivation blocked the memory trace the somatosensory CS. The finding further supports the view that IPN-mediated memory trace formation is not dependent on the modality of the CS.
Animals↗
Neuroprotective role of S12024 against neurodegeneration in the rat dentate gyrus.
We assessed the neuroprotective capabilities of S12024 (R,S 1-methyl 8-(2-morpholinylmethoxy)-1,2,3,4-tetrahydroquinoleine methane sulphonate) in a model of neuronal degeneration in the dentate gyrus of the rat hippocampus. Specific degeneration of a large part of neurons in the lateral blade of the gyrus dentatus occurred after small intrahippocampal injections of water with or without amyloid-beta 1-28 fragment. S12024 reduced the number of animals with neuronal loss in the hippocampus, diminished the extent of the lesion, and reversed deficits of passive avoidance learning acquisition in animals with deposits of amyloid-beta 1-28. These results suggest that S12024 has neuroprotective effects on hippocampal cells and that the neurodegeneration by fluid injection combined with deposit of amyloid-beta 1-28 may be used to assay the neuroprotective activity of pharmacological compounds.
Amyloid beta-Peptides↗
Influence of tab and disk design on shade matching of dental porcelain.
STATEMENT OF PROBLEM: Given the complexity of tooth color, the variations of shade within each tooth, and translucency, it is difficult to view only one small area and select a shade match for restorations. PURPOSE: This study tested the effect of specimen design on porcelain shade matching, hypothesizing that flat disks would be matched to one another with more accuracy than tooth-shaped tabs to tabs. MATERIALS AND METHODS: All testing was conducted in a Macbeth SpectraLight booth with D65 illumination. Seventy-three senior dental students (25 women and 48 men; mean age, 27 years) were asked to match selected Vita porcelain disks and Vita shade tabs to like specimens. The design order, namely matching tabs or disks first, was alternated for each observer. The specimens were handed to the observer individually. No time limit for matching was imposed, although each observer was given explicit instructions related to the observation and handling of the specimens. Upon completion of the matching exercises, each student received his or her standardized test results and reviewed the matching results. The time for testing and review was approximately 20 minutes per observer. An analysis of variance, with gender and order as 2 factors that could affect matching scores, was performed (P <.05). RESULTS: The mean matching scores were 78.4% for disks and 73.6% for tabs (P=.119). Female observers matched 76.5% of the disks and 77.5% of the tabs, whereas male observers matched 79.4% of the disks and 71.6% of the tabs (P=.054). Matching disks before tabs yielded equivalent levels of shade matching (disks, 77.6%; tabs, 77.1%). When tabs were matched first, the scores were as follows: disks, 79.8%, and tabs, 67.3% (P=.010). CONCLUSIONS: Within the limitations of this study, there was no significant difference in shade-matching accuracy between the 2 shapes, although the order of design matching resulted in a difference in shade-matching ability. When tabs were matched first and disks second, improved matching was evident on the second test. The reverse was not true; no learning was demonstrated when the tabs were matched after the disks.
Adult↗
Protective effect of Rosa laevigata against amyloid beta peptide-induced oxidative stress.
The amyloid beta (Abeta) peptide is known to increase free radical production in nerve cells, leading to cell death. To investigate the effect of Rosa laevigata against Abeta-induced oxidative damage, in vitro assays and in vivo behavioral tests were performed. R. laevigata showed cell protective effects against oxidative stress-induced cytotoxicity. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reduction assay exhibited significant increase in cell viability when rat pheochromocytoma (PC 12) cells were treated with R. laevigata extracts. Administration of R. laevigata extracts to mice significantly reversed the Abeta-induced learning and memory impairment in in vivo behavioral tests. These results suggest that R. laevigata extracts can reduce the cytotoxicity of Abeta in PC 12 cells, possibly by the reduction of oxidative stress, and these extracts may be useful in the prevention of Alzheimer's disease.
Amyloid beta-Peptides↗
Zilascorb(2H), a low-toxicity protein synthesis inhibitor that exhibits signs of anticancer activity in malignant melanoma.
Zilascorb(2H) is a benzaldehyde derivative giving rise to strong protein synthesis inhibition. It has shown antitumor activity against human malignant melanoma grown as xenografts in nude mice. The effect was manifest only after prolonged daily treatment and was quickly reversible when treatment was stopped. Drug-induced fever was the dose-limiting toxicity observed during clinical phase I studies of zilascorb(2H). The object of the present study was to assess antitumor activity, safety and tolerability of the drug in melanoma patients. Sixteen patients with disseminated malignant melanoma were included, all presenting with WHO performance status 0-2 and adequate organ functions. Previous chemo- or radiotherapy was accepted, while patients with known CNS metastases were excluded. Due to its low solubility and quickly reversible activity, zilascorb(2H) 1400 mg was infused by the patients twice daily through a venous access port for up to 12 weeks. Induction of tumor regression was demonstrated in one patient, who was, however, withdrawn from treatment after 2 weeks because of recurrent fever and fatigue. All the 12 patients evaluable for antitumor activity had progressive disease. Zilascorb(2H) was well tolerated, except for fever reactions and reversible liver toxicity. Most patients learned quickly how to handle a venous access port, but daily self-administration of i.v. infusions became too cumbersome to justify further patient inclusion despite the tumor regression observed. We conclude that zilascorb(2H) seems to have the potential for antitumor activity in metastatic malignant melanoma and is well tolerated. Daily self-administration of drug infusions is not desirable for long periods and zilascorb(2H) tablets have been developed. Because of its favorable toxicity profile, especially compared to other protein synthesis inhibitors, zilascorb(2H) may be particularly interesting for combinations with other anticancer drugs.
Adult↗
Potential nootropic agents, 4-alkoxy-2-(1-piperazinyl)quinazoline derivatives.
A series of 4-alkoxy-2-(1-piperazinyl)quinazoline derivatives was synthesized and evaluated for its ability to reverse a scopolamine-induced learned impairment in a one-trial passive avoidance task (antiamnestic activity). 2-(4-Allyl-1-piperazinyl)-4-pentyloxyquinazoline (4) showed more potent antiamnestic activity than such reference compounds as aniracetam, idebenone and bifemelane at a wide dose range (1-30 mg/kg]. Compound 4 also exhibited potent anticonvulsive and antihypoxic activities, and was selected as the most promising nootropic candidate agent.
Animals↗
Antidepressant effects of tricyclic antidepressants and selective serotonin-uptake blockers in diabetic rats.
Because it was reported that diabetic rodents were resistant to the effects of several tricyclic antidepressants in various psychopharmacological models, we decided to test the hypothesis that the serotonergic dysfunction seen in diabetes might participate in this phenomenon. The ability of three serotonin-uptake blockers to reverse the performance deficit in learning induced by previous uncontrollable stress (learned-helplessness paradigm) was investigated in streptozocin-induced diabetic rats. Three weeks after induction of diabetes, rats were subjected to a session of 60 inescapable electric foot shocks and, after 48 h, to three daily sessions of two-way shuttle-box training. Three serotonin-uptake blockers were given intraperitoneally over 5 consecutive days. As with nondiabetic rats, citalopram (1 mg.kg-1. day-1), fluoxetine (2 and 4 mg.kg-1. day-1), and fluvoxamine (4 mg.kg-1.day-1) reduced the number of escape failures in diabetic rats. From these data, we suggest that it is unlikely that the impaired response of diabetic rats to tricyclic antidepressants is caused by serotonergic dysfunction.
Analysis of Variance↗
Reversal of stable behavioural modifications through NMDA receptor inhibition in rats.
In order to study the effect of long-term dizocilpine infusion on memory, two different paradigms of stably modified behaviour were used in rats. The first was the escape deficits (ED) induced and maintained either by repeated daily administrations of SKF 38393, a rather selective D1 dopamine receptor agonist, or by repeated stress; the second was sensitisation to the effect of cocaine on motility. Fluoxetine (FLX), imipramine (IMI) and clomipramine (CMI) were equally effective in reversing the reduced reactivity of animals in both ED models. Dizocilpine showed a similar efficacy to that of classic antidepressants on the pharmacologically-induced ED, but failed to affect the stress-induced ED. In rats previously sensitised to cocaine and then infused with dizocilpine for 7 days after suspension of cocaine administration, the state of sensitisation, remained intact; however, in animals receiving dizocilpine plus a concomitant daily injection of cocaine, dizocilpine significantly reduced cocaine sensitisation. These results potentially suggest a new approach to the treatment of drug addiction and other psychiatric disorders. Finally, it was concluded that NMDA receptor blockade not only prevents, but also reverses many, if not all, learned behaviours, and that this phenomenon differs from the effect of antidepressants.
Journal Article↗
Pharmacological activities and mechanisms of natural phenylpropanoid glycosides.
The pharmacological activities and mechanisms of action of natural phenylpropanoid glycosides extracted from a variety of plants are summarized in this review, such as antitumor, antivirus, anti-inflammation, antibacteria, antiartherosclerosis, anti-platelet-aggregation, antihypertension, antifatigue, analgesia, hepatoprotection, immunosuppression, protection of sex and learning behavior, protection of neurodegeneration, reverse transformation of tumor cells, inhibition of telomerase and shortening telomere length in tumor cells, effects on enzymes and cytokines, antioxidation, free radical scavenging and fast repair of oxidative damaged DNA. Molecular modeling is discussed as well as structure-activity relationships.
Animals↗
Learning, retention and generalization of a mirror tracing skill in Alzheimer's disease.
The present study examined the ability of 12 patients with probable Alzheimer's disease (AD) and 12 age- and education-matched normal control (NC) subjects to learn and retain the visuomotor skills necessary to efficiently trace a pattern (e.g., a 4- or 6-pointed star) seen only in mirror-reversed view. Those AD (N=6) and NC (N=7) subjects who were able to initially perform the basic mirror tracing task did not differ significantly in initial level of performance, learning over trials, retention of the skill over a 30-min delay interval, and generalization of the skill to a new figure or to the opposite direction of tracing. The AD patients who were unable to initially perform the mirror tracing task were significantly worse than those who could perform the task on several neuropsychological measures sensitive to deficits in problem solving and executive functions, but not on tests of global cognitive decline, memory, language, or visuoperceptual functioning. These results indicate that acquisition and retention of a complex visuomotor skill can proceed normally in the early stages of AD in those individuals who can initially perform the basic task, and that inability to perform the basic task may be related to the frontal lobe dysfunction that is often prominent in the disorder.
Aged↗