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Biomedical subjects

C Mondadori

Publications and source records attributed to C Mondadori.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Involvement of a steroidal component in the mechanism of action of piracetam-like nootropics.

Since adrenalectomy abolishes the memory-enhancing effects of piracetam and its derivatives, oxiracetam, aniracetam and pramiracetam, the question arises whether endogenous steroids play a role in their mechanism of action. We show that inhibition of steroid biosynthesis by aminoglutethimide and blockade of the aldosterone receptors by epoxymexrenone completely suppress the memory-improving effects of the nootropics. These results indicate that steroids, or, more precisely, activities mediated by the aldosterone receptors, might be involved in the mechanism of action of this class of nootropics. Blockade of aldosterone receptors, however, does not block the effects of cholinomimetics on memory, indicating the involvement of another mechanism of action.

Aminoglutethimide↗
PubMed1990

Nootropic effects of ACE inhibitors in mice.

The angiotensin converting enzyme (ACE) inhibitors captopril and enalapril and the nootropic piracetam reduced the amnesiogenic effects of cerebral electroshock treatment in mice. These compounds also directly improved passive-avoidance learning if administered before the learning trial. When given immediately after the learning trial, captopril and piracetam were active, but not enalapril. Captopril, but neither enalapril nor piracetam, facilitated memory retrieval after a 2-month retention interval. Unlike those of piracetam, the memory-improving effects of captopril and enalapril are not established by aldosterone-receptor blockade, suggesting that the two types of drug act via different mechanisms of action.

Adrenalectomy↗
PubMed1989

NMDA receptor antagonists can enhance or impair learning performance in animals.

The effects of NMDA receptor antagonism on learning and memory were investigated using competitive (DL-2-amino-7-phosphonoheptanoate, AP7) and non-competitive (MK 801) blockers in three different learning tasks. Administration (i.p.) of drugs prior to training resulted in impaired learning performance in the place-navigation and dark-avoidance paradigms, and improved performance in the step-down passive avoidance task; however, using this treatment protocol, the possibility of drug-induced non-mnemonic effects modifying learning performance could not be excluded. Drug administration immediately post-trial had no effect in the place-navigation paradigm, and improved retention performance in the dark-avoidance and step-down avoidance tasks. The similar results obtained with both types of antagonist indicate that the observed effects are indeed due to NMDA receptor blockade, and hence that such blockade modifies learning in a task-dependent manner. Exclusion of non-mnemonic effects by using the post-trial treatment regime demonstrates that NMDA antagonists facilitate learning of passive avoidance tasks.

2-Amino-5-phosphonovalerate↗
PubMed1989

Neural plasticity in vivo: opioid sensitivity of memory develops gradually after a septal lesion.

Neuronal plasticity can manifest itself in alterations in the sensitivity of memory to the effects of drugs. After the production of a brain lesion, the memory processing of a passive-avoidance task in mice gradually becomes sensitive to the effect of morphine, i.e., an improvement in retention performance is seen after 6 weeks, but not after 1 or 2 weeks. The results presented demonstrate that, even if they lead to no discernible changes in behaviour, plastic processes can still be detected by means of behavioural tests.

Animals↗
PubMed1989

The effects of nootropics on memory: new aspects for basic research.

The mechanism through which nootropics of the piracetam type (i.e., piracetam itself and its analogues oxiracetam, pramiracetam, and aniracetam) improve memory is still uncertain. Its elucidation will, however, not only mark an advance in the treatment of cognitive disorders, but also shed light on the basic processes of memory storage. Although the great majority of the findings available so far seem to suggest cholinergic mechanisms, divergent results are obtained whenever parallel experiments are performed with two or more of these compounds. More recent observations indicate that interactions with steroids take place. All four compounds are inactive in adrenalectomized laboratory animals; chemical blockade of the adrenal cortex with aminoglutethimide and pretreatment which epoxymexrenon, a potent mineralocorticoid antagonist, eradicated the memory-enhancing effect of all four substances.

Animals↗
PubMed1989

Cardiac responses to head up tilt during early extrauterine life: relevance of active acquisition of erect posture.

Mammals must adapt to gravity on passing from the intrauterine to the extrauterine environment. In order to evaluate the cardiovascular effects of gravity in the first phases of extrauterine life, the effects of passive orthostatism on the cardiac filling volume were investigated through longitudinal haemodynamic studies in 14 normal healthy males before (6 months) and after (18 months) acquiring the ability to stand. Left ventricular diameter (by echocardiographic measurement), arterial blood pressure (by sphygmomanometry) and heart rate were measured in the supine and upright position at both ages. At 6 months the left ventricular end diastolic volume was not modified by a change in posture [supine 6(SEM 3) ml, upright 6(3) ml], so heart rate was minimally altered [supine 128(9), upright 130(11) beats.min-1] and blood pressure remained stable [supine 74(6), upright 73(5) mm Hg]. After the acquisition of the erect posture (18 months) left ventricular end diastolic volume was reduced [supine 14(3), upright 8(2) ml], heart rate increased [supine 110(11), upright 127(12) beats.min-1] and blood pressure remained constant [supine 80(6), upright 79(7) mm Hg]. The assumption of the erect posture therefore represents a phase when, for the first time in the natural history of the cardiovascular system, translocation of intravascular volume from the cardiopulmonary area to the periphery stimulates nervous and humoral responses to control the dynamics of body fluids and arterial blood pressure in a gravitational environment.

Adaptation, Physiological↗
PubMed1989

Marked blood pressure fluctuations during narcoleptic attacks alternating with abnormal wakefulness: effects of treatment with clonidine.

A middle-aged man was admitted to our department because of sleep-wake cycle disorders (alternating hypersomnia and sleeplessness), bipolar behavioural disturbances and marked fluctuations in blood pressure and heart rate. Neither evident precipitating stimuli nor an obvious cause for his illness were found. When tests that normally activate intrinsic autonomic responses were performed, two distinct circulatory patterns were recognized. During hypersomnia (phase A), cardiovascular reflex activity was blunted or abolished and orthostasis could not be maintained. The clinical, biochemical, behavioural pictures and the observed decrease in sympathetic outflow resembled the effects of clonidine administration. On the contrary, during sleeplessness (phase B) the autonomic pathways were functionally integral and orthostatic hypotension was not detected. The clinical, biochemical, behavioural features and cardiovascular overactivity closely mimicked the abrupt withdrawal syndrome encountered with clonidine. Three hypothetical mechanisms are advanced to explain this intriguing case as well as the acute and chronic relief of our patient's clinical problem following institution of clonidine therapy (phase C). The role played by central alpha adrenoceptors in integrating sleep-wake, cardiovascular and behavioural functions is also suggested.

Blood Pressure↗
PubMed1988

Cardiogenic hypertension in maturing dogs.

The purpose of this study was to evaluate whether the heart can induce high blood pressure by maintaining an inappropriately elevated cardiac output/body weight ratio during growth. Direct (femoral artery) mean arterial pressure (MAP), heart rate, cardiac output/body weight ratio (as defined by M-mode echocardiography), and total peripheral vascular resistance were measured and calculated every 2 months in nine conscious dogs during development from 2 to 10 months of age. In four dogs a J-shaped catheter for atrial pacing was chronically implanted at the age of 3 months, and their hearts were permanently paced at 130 beats/min until maturity. The aim of atrial pacing was to prevent the natural slowing of the heart rate and, consequently, to maintain a cardiac output/body weight ratio that was inappropriately high in relation to age during growth. Five dogs were studied as controls. No hemodynamic differences were observed until the age of 4 months. From the age of 5 to 10 months heart rate was kept at 130 beats/min by atrial pacing in the atrially paced group, and the mean cardiac output/body weight ratio did not decrease (196 +/- 24 vs 191 +/- 34 [SE] ml/min/kg). MAP rose from 62 +/- 4 to 116 +/- 8 mm Hg, and total peripheral resistance increased from 0.34 +/- 0.07 to to 0.61 +/- 0.09 mm Hg/ml/min/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist.

CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid) was found to be a potent, stereospecific inhibitor of N-methyl-D-aspartate (NMDA)-evoked, but not KCl-evoked, [3H] acetylcholine release from slices of the rat striatum. The concentration-response curve to NMDA was shifted to the right by CGS 19755 (pA2 = 5.94), suggesting a competitive interaction with NMDA-type receptors. CGS 19755 inhibited the binding of [3H]-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid to NMDA-type receptors with an IC50 of 50 nM, making it the most potent NMDA-type receptor antagonist reported to date. CGS 19755 failed to interact with 23 other receptor types as assessed by receptor binding, including the quisqualate- and kainate-type excitatory amino acid receptors. In crude P2 fractions, no evidence was obtained to suggest that CGS 19755 is taken up by an active transport system. Furthermore, CGS 19755 failed to affect the uptake of L-[3H]glutamate, or to interact with aconitine-induced inhibition of L-[3H]glutamate uptake, the latter finding suggesting a lack of membrane-stabilizing or local anesthetic properties. CGS 19755 selectively antagonized the excitatory effect of iontophoretically applied NMDA in the red nucleus of the rat without affecting the excitatory effects of quisqualate. CGS 19755 blocked the harmaline-induced increase in cerebellar cyclic GMP levels at a dose of 4 mg/kg i.p. with a duration of action exceeding 2 hr. CGS 19755 inhibited convulsions elicited by maximal electroshock in rat (ED50 = 3.8 mg/kg i.p. 1 hr after administration) and in mouse (ED50 = 2.0 mg/kg i.p. 0.5 hr after administration). Likewise, convulsions elicited by picrotoxin were inhibited by CGS 19755, whereas the compound was relatively weak in protecting against convulsions elicited by pentylenetetrazole or strychnine. CGS 19755 produced retention performance deficits in a dark avoidance task. However, CGS 19755 did not show a unique propensity for learning and memory disruption compared to other anticonvulsants.

Acetylcholine↗