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C Mondadori

Publications and source records attributed to C Mondadori.

10 recordsLinked to original sources

Elevated corticosteroid levels block the memory-improving effects of nootropics and cholinomimetics.

Oral pretreatment of mice with aldosterone or corticosterone blocked the memory-enhancing effects of piracetam, pramiracetam, aniracetam and oxiracetam in a dose-related manner, without, however, impairing the animals' learning performance. The improvement of memory induced by physostigmine, arecoline, and tacrine (THA) was similarly inhibited. The fact that elevated steroid levels suppress the memory-enhancing effects of entirely different substances could indicate that these substances have a common site of action. In the light of new observations showing increased cortisol concentrations in Alzheimer patients, this steroid dependency of the effects of memory enhancers might explain why only a limited number of these patients respond to therapy with nootropics or cholinomimetics.

Adrenal Cortex Hormones

Pretreatment with aldosterone or corticosterone blocks the memory-enhancing effects of nimodipine, captopril, CGP 37,849, and strychnine in mice.

Oral pretreatment with aldosterone or corticosterone blocked the memory-enhancing effects of the calcium antagonist nimodipine, the ACE inhibitor captopril, the NMDA blocker CGP 37,849, and the glycine antagonist strychnine in a passive-avoidance test in mice. The memory-disturbing effects of phenobarbitone, diazepam, CGP 37,849 and scopolamine were not influenced by the hormonal pretreatment. These findings could indicate the involvement of a steroid-sensitive mechanism in drug-induced improvement of memory. In the light of clinical observations showing elevated cortisol levels in Alzheimer patients, the results might also explain why only a limited number of these patients respond to therapy with memory enhancers.

2-Amino-5-phosphonovalerate

CGS 5649 B, a new compound, reverses age-related cognitive dysfunctions in rats.

CGS 5649 B improves the learning performance of aged rats in a one-way active-avoidance situation. If, under reversed conditions, treated aged rats are also tested for passive avoidance, they show "place learning," which our findings have demonstrated to be typical of young rats. The effects of the substance are not confined to these experimental models nor are they species specific: it also facilitates passive avoidance in mice and social learning in rats. The compound is effective if administered before or immediately after the learning trial.

Aging

Adrenalectomy, corticosteroid replacement and their importance for drug-induced memory-enhancement in mice.

Adrenalectomy blocks the memory-improving effect of piracetam-like compounds in mice. If this blockade is due to the removal of endogenous corticosteroids, replacement therapy with exogenous corticosteroids should reinstate the effects on memory. The present experiments were designed to determine the appropriate replacement dose (concentration in the drinking fluid) for corticosterone and aldosterone, the main corticosteroids in mice. Based on the effects of corticosterone on thymus weight, replacement with 3 micrograms/ml corticosterone given in the drinking fluid (0.9% NaCl) for one week was found to be appropriate. The appropriate replacement dose for aldosterone was found by giving aldosterone to adrenalectomized (ADX) mice in the drinking fluid in combination with 3 micrograms/ml corticosterone. The combination of 3 micrograms/ml corticosterone + 30 ng/ml aldosterone resulted in a plasma ratio of corticosterone/aldosterone which most closely approximated the ratio seen in sham-ADX control animals. The physiologic adequacy of the corticosteroid replacement doses resulting from this study were clearly demonstrated in subsequent behavioral experiments where blockade of the memory-enhancing effects of piracetam by adrenalectomy were overcome by replacement with either 3 micrograms/ml corticosterone or 30 ng/ml aldosterone given in the drinking fluid.

Adrenalectomy

How long does 'memory consolidation' take? New compounds can improve retention performance, even if administered up to 24 hours after the learning experience.

The 'nootropics' are a new class of psychoactive substances that improve learning and memory. Their almost exclusive effect on memory may indicate that they act on processes specifically involved in information storage. When administered after the learning trial, these substances improve subsequent retention performance in mice, even if an interval of 8 h has elapsed between learning and treatment. CGS 5649B, a highly active new substance, is effective even after an interval of 24 h. Although consonant with the 'consolidation' hypothesis, the results may challenge prevailing notions about the formation of memory traces.

Animals

MK-801 can facilitate passive avoidance memory when retention is not present in control animals, and can fail to facilitate when it is present.

The results confirm that NMDA receptor blockade can result in improved retention performance of mice in step-down passive avoidance. A series of behavioural variations and analyses revealed that memory in the task depended mainly on the appearance of the grid that had been associated with shock, rather than on the execution of an instrumental response or on the spatial locus of the punishment. When the grid was made invisible during retest, retention was never found. However, MK-801 did not facilitate retention based on the appearance of the grid. In contrast, conditions were found in which, even though control animals showed no learning, MK 801 given after the learning trial facilitated retention. Thus, the dominant mode of learning and memory in the step-down task is insensitive to the drug, whereas the drug raises a weaker or alternative mode to above threshold levels.

Animals

Facilitation of memory processing by posttrial morphine: possible involvement of reinforcement mechanisms?

Posttrial administration of 40 mg/kg and 100 mg/kg, but not of 1 mg/kg, of morphine hydrochloride facilitates learning of a one-trial passive avoidance task in drug-naive mice. The effect does not depend on the punishing properties of the morphine injection, since in injection of LiCl (a strong punisher) fails to enhance learning in a similar way. After the establishment of tolerance by several morphone administrations, the 100 mg/kg, but not the 40 mg/kg, dose level resulted in memory facilitation. The data are discussed in connection with the hypothesis that morphine acts directly on reinforcement mechanisms by activating the opiate receptor.

Animals