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Biomedical subjects

R Chermat

Publications and source records attributed to R Chermat.

At least 19 recordsLinked to original sources
PubMed1991

Microtubule disruption and cognitive defects: effect of colchicine on learning behavior in rats.

Neuropathological findings in Alzheimer's disease (AD) suggest a possible involvement of microtubule dysfunction in neurodegenerative process pathogenesis. Because microtubules have a major role in neuronal plasticity, microtubule disruption could be also directly responsible for cognitive defects in AD. We report that in rats, continuous microtubule disruption induced by chronic colchicine administration results in a dose-dependent learning deficit. In addition, retention is also impaired. These cognitive defects are specific, as chronic colchicine induces no other behavioral toxicity within the study dose range. Colchicine-induced cognitive defects resemble those of AD, which are characterised by amnesia of recent learning and loss of formerly established memories. This new procedure of pharmacologically induced cognitive impairment may prove useful, both towards understanding AD pathogenesis and towards drug screening.

Animals↗
PubMed1988

Specificity of piracetam's anti-amnesic activity in three models of amnesia in the mouse.

The effects of piracetam on the amnesias induced by scopolamine, diazepam and electroconvulsive shock (ECS) were studied in a passive avoidance procedure in the mouse and compared with the interactions of piracetam with the major behavioral effects of these treatments, namely scopolamine-induced hyperactivity, diazepam-induced release of punished behavior (Four Plates Test) and ECS-induced convulsions. Amnesia was induced by injecting scopolamine or diazepam (1 mg/kg, IP) 30 minutes before or applying ECS immediately after the first session (S1) of the passive avoidance task. Piracetam was studied at 3 doses (512, 1024 and 2048 mg/kg) administered PO 60 minutes before S1. Retention was measured 24 hours later (S2) in the absence of any treatment. Piracetam dose-dependently attenuated the memory deficits induced by the three amnesic treatments but did not affect either scopolamine-induced hyperactivity, diazepam-induced release of punished behavior or ECS-induced convulsions. These results point to the specificity of piracetam's anti-amnesic activity and, in particular, suggest that piracetam can suppress the memory disturbances induced by diazepam without affecting diazepam's anxiolytic activity. The test battery employed would therefore seem highly suitable for evaluating the potential nootropic activity of novel compounds.

Amnesia↗
PubMed1987

Comparing benzodiazepines using the staircase test in mice.

Eleven benzodiazepines were evaluated in the staircase test in mice. The behavioural parameters measured were the number of steps climbed and the number of rears during a 3-min test. Climbing and to a lesser extent rears were enhanced at low doses, whereas both parameters, particularly rearing, were reduced at higher doses. The differential effects of the drugs on the two parameters were used to determine indices of anxiolytic efficacy for each drug where increases in climbing were taken to indicate the onset of anxiolytic activity and decreases in rearing the onset of sedative activity. The compounds could be ranked according to these indices in a manner which appears to reflect their therapeutic profile in man.

Animals↗
PubMed1987

The automated Tail Suspension Test: a computerized device which differentiates psychotropic drugs.

1. Mice when suspended by the tail will alternate between active attempts to escape and immobility. Immobility like that measured in the behavioral despair test is reduced by a wide variety of antidepressant agents. 2. The present paper describes a computerized version of this test (ITEMATIC-TST) which in addition to recording immobility measures the power of the movements. 3. Various tricyclic (amitriptyline, desipramine, imipramine), MAOI (clorgyline, moclobemide, nialamide, pargyline, toloxatone) and atypical antidepressants (bupropion, citalopram, indalpine, mianserin, nomifensine, viloxazine) were tested and compared with psychostimulants (d-amphetamine, caffeine), neuroleptics (chlorpromazine, haloperidol, sulpiride), anxiolytics (clobazam, diazepam) and agents acting on the cholinergic system (atropine, oxotremorine). 4. All antidepressants decreased the duration of immobility and most increased the power of movements. 5. The psychostimulants also decreased immobility but only amphetamine increased the power of movements. 6. Neuroleptics increased immobility without affecting the power of movements, whereas anxiolytics increased immobility but decreased the power of movements. 7. Atropine had a profile similar to antidepressants whereas oxotremorine tended to have opposite effects. 8. The results suggest that the automated test system with its two parameters is not only sensitive to antidepressants but could also be useful for generating activity profiles for different kinds of psychotropic agent.

Animals↗
PubMed1987

Use of the automated tail suspension test for the primary screening of psychotropic agents.

Mice, when suspended by the tail, will alternate between active attempts to escape and immobility. A specially developed computerized device (ITEMATIC-TST) automatically measures the duration of immobility of 6 mice at one time and at the same time provides a measure of the energy expended by each animal, the power of the movements. Use of these 2 parameters enables activity profiles to be generated which can distinguish different classes of psychotropic activity. Immobility is decreased by antidepressants and psychostimulants, but increased by neuroleptics and minor tranquillizers. Minor tranquillizers can be distinguished from neuroleptics in that they decrease the power of the movements, whereas neuroleptics are without effect on this parameter. The present experiments were undertaken to see whether the activity profiles generated in this procedure could indeed be useful for primary psychotropic screening. Eighteen compounds, including antidepressants, neuroleptics, minor tranquillizers, sedative/hypnotics, dopaminergic stimulants and 3 dummy compounds were first submitted to a shortened primary observation procedure for dose finding and were then investigated at 2 doses in the automated tail suspension test. All experiments were conducted blind. The results obtained largely confirm the activity profiles already reported in this test and show that the combined use of primary observation and the automated tail suspension test permit the unambiguous identification of the pharmacological activity of 15 of the compounds tested with tentative identification of the 3 remaining compounds.

Animals↗
PubMed1986

Antidepressant-like effects of diphenylhydantoin in mice: involvement of alpha-adrenoceptors.

Several studies have indicated that alpha-adrenergic systems are implicated in the anticonvulsant activity of diphenylhydantoin. We now report that in mice prazosin (0.125 mg/kg), a blocker of alpha 1-adrenoceptors, reverses the effects exerted by diphenylhydantoin (256 mg/kg) in tests which are predictive of antidepressant activity: reserpine-induced ptosis and immobility which are caused by inescapable, aversive situations. These date indicate that alpha-adrenoceptors are not only involved in the anticonvulsant action of diphenylhydantoin, but also in its antidepressant-like effects.

Animals↗
PubMed1986

Comparative study in mice of ten 1,4-benzodiazepines and of clobazam: anticonvulsant, anxiolytic, sedative, and myorelaxant effects.

We will present data from the comparison between four tests in mice of 10 1,4-benzodiazepines and one 1,5-benzodiazepine (clobazam). The tests used were: the "4 plates test" of anxiolytic activity; the electroshock test to determine the anticonvulsive effects; actimetry to predict the sedative effect on motricity; and traction test to predict the myorelaxant effect. The latter two tests have been suggested to be predictive of side-effects that damage psychomotor efficiency in human patients. A comparison of ED50s determined from the predictive tests of the therapeutic effect and those of the side-effects led to the calculation of ratios considered to be predictive of the safety margin. A classification according to this margin shows the advantages of the 1,5-benzodiazepine compared with the 1,4-benzodiazepines. Despite the caution needed in the extrapolation of the results from animals to humans, this work stresses the interesting place that the 1,5-benzodiazepine seem to hold as anticonvulsant in clinical practice.

Animals↗
PubMed1979

[Effects of four beta-blocking agents on some psychopharmacological tests in mice (author's transl)].

Common effects of four beta-adrenergic blocking drugs have been investigated in mice using classical and new psychopharmacological tests. Propranolol, alprenolol, practolol and penbutolol reduced the increase in locomotor activity produced by reserpine after MAO inhibition; they produce hypothermia when associated with amphetamine and they increase oxotremorine-induced hypothermia. Regarding these three tests the studied substances ranged themseleves in the same order of potency: penbutolol greater than propranolol greater than alprenolol greater than practolol. Propranolol and penbutolol decreased the toxicity provoked in crowded mice by amphetamine or by the association pargyline-reserpine; alprenolol and practolol did not. Propranolol, penbutolol and alprenolol antagonized the amphetamine-induced increase in motor activity; practolol did not. When used at doses for which d-l propranolol was active, the dextrogyre isomer of propranolol was without effect whatever the test studied. It is suggested that for the selection of a beta-blocking drug, regarding central effects in man, the tests described would deserve consideration.

Adrenergic beta-Antagonists↗
PubMed1979

Amoxapine in experimental psychopharmacology: a neuroleptic or an antidepressant?

2-Chloro-11-(piperazinyl)dibenz[b,f][1,4]-oxazepine (amoxapine) gives an unusual spectrum in psychopharmacological tests. Many of its effects are similar to those of neuroleptics: sedation, decrease in motor activity, catalepsy (which is, however, qualitatively different from that induced by classical neuroleptics), transitory suppression of avoidance reaction, antagonism of amphetamine induced toxicity in crowded mice and inhibition of stereotyped behavior induced by amphetamine in rats, and antagonism to various effects of apomorphine (stereotyped behaviour in rats, climbing behaviour, stereotyped behaviour and hypothermia in mice). At similar doses which produce the above mentioned effects, amoxapine also shows effects atypical for a neuroleptic, but which are relatively characteristic of antidepressants: antagonism of prochlorperazine-induced catalepsy in rats, inhibition of reserpine induced hypothermia in mice and enhancement of yohimbine toxicity in mice. The profile of this substance does not facilitate the anticipation of therapeutic effects in humans.

Amoxapine↗
PubMed1978

[Models of inhibition in animal behavior].

The concept of inhibition in psychopharmacology is discussed by presenting different models of behavioral inhibition in animals. The inhibitions induced by fear or anxiety appear as a result of punishment introduction into an unknown situation, frustration... These inhibitions are particularly sensitive to minor tranquilizers. The inhibitions induced by "fatigue" appear when avoidance situations continue for 24 hours or when a situation demands a marked increase of animal activity to obtain the same reward (food). These inhibitions are particularly sensitive to psychoanaleptics. The inhibition induced by placing a animal in an inescapable situation is particularly sensitive to antidepressants.

Animals↗
PubMed1976

Interaction of atropine or methylatropinium with four effects of two cholinergic drugs.

In mice, pilocarpine - or oxotremorine - induced decrease in locomotor activity and increase of the reaction time to pain were antagonized by atropine and not by methylatropinium. Identical doses of atropine and methylatropinium suppressed the antagonism of the cholinergics towards reserpine-induced palpebral ptosis. Cholinergics-induced hypothermia was not clearly antagonized by atropine or methylatropinium.

Animals↗