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Biomedical subjects

R D Porsolt

Publications and source records attributed to R D Porsolt.

At least 37 records · Page 2Linked to original sources
PubMed1987

The effects of exifone, a new agent for senile memory disorder, on two models of memory in the mouse.

The effects of exifone (ADLONE), hexahydro-2,3,4,3',4',5'-benzophenone, were tested in two models of memory in the mouse: habituation of exploratory activity and antagonism of amnesia induced by scopolamine in a passive avoidance task. In the first model, mice which had received exifone (128 and 256 mg/kg IP) 30 minutes before a 3 minute exposure to a staircase exploratory test showed a more marked decrease in exploratory activity in the same apparatus 24 hours later (habituation) than a control group indicating improved memory. Similar results were obtained with piracetam (512 mg/kg, IP). In the second model exifone (512 mg/kg PO), administered 60 minutes before both the learning and retention trials of a standard step-through passive avoidance, task partially antagonized the amnesia induced by 10 mg/kg scopolamine IP administered immediately after the learning trial. Similar results were obtained with piracetam (800 mg/kg PO). Taken together these results suggest that exifone facilitates memory function in simple rodent models in a manner consistent with its supposed therapeutic effects in man.

Amnesia↗
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

Psychopharmacological profile of the new cognition enhancing agent exifone in the mouse.

Hexahydro-2,3,4,3',4',5'-benzophenone (exifone, Adlone), a novel compound proposed for treating cognitive dysfunction in geriatric patients, was tested in a battery of standard psychopharmacological tests in the mouse. The results indicated that the compound was non-toxic and induced no signs of overt stimulation or sedation after acute administration of oral doses up to 1024 mg/kg. The compound was devoid of anxiolytic, anticonvulsant or classical neuroleptic activity and did not antagonize the effects of reserpine or a high dose of apomorphine, two tests indicative of classical antidepressant activity. On the other hand, exifone clearly decreased the duration of immobility in the tail suspension test and antagonized the hypothermia induced by a low dose of apomorphine. The compound shortened the duration of barbital induced sleep without affecting the duration of sleep induced by pentobarbital. The effects observed suggest that exifone is not devoid of psychotropic activity and might possess some properties of an atypical antidepressant.

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↗
PubMed1984

Discrimination of the amphetamine cue. Effects of A, B and mixed type inhibitors of monoamine oxidase.

Rats were trained to discriminate between the effects of 0.6 mg/kg of (+)-amphetamine given intraperitoneally saline in a two-lever operant task, according to a fixed ratio ( FR10 ) schedule of food reinforcement. Once trained (greater than 90% responding on the appropriate lever during sessions with drug and saline, respectively over 2 weeks), they were given tests of generalization with various type A, type B or mixed type monoamine oxidase inhibitors (MAOI). Generalization was tested during the first 100 sec of a 15 min trial during which no reinforcements were given (extinction) followed by reinforcement on both levers for the rest of the session. Generalization to amphetamine was estimated using both the percentage of responding on the "drug lever" and a measure of choice of lever. None of the type A MAOI's tested [ cimoxatone (MD 780515), clorgyline, LY 51641, moclobemide (Ro 11-1163), toloxatone] showed generalization towards the lever for amphetamine. Clear or partial amphetamine-like responding was observed with the B type MAOI (+/-)-deprenyl and LY 54761 but not with two other type B MAOI's MD 240928 or pargyline. (+/-)-Tranylcypromine, but not nialamide (mixed type MAOI's), induced dose-dependent responding on the lever for amphetamine. It was concluded that amphetamine-like activity was not an intrinsic property of A or B type MAOI's.

Amphetamine↗
PubMed1984

Effects of imipramine on separation-induced vocalizations in young rhesus monkeys.

Three Rhesus monkeys were removed from their mothers at birth and reared together in a group cage. When they were one year old they were subjected to repeated separations during which they were placed alone for 1 hour in another cage in an acoustically isolated adjacent room. The number of vocalizations and gross body movements were recorded automatically. Single injections of imipramine (3.75, 7.5 and 15 mg/kg IM) instead of decreasing tended to increase the number of vocalizations without affecting motor activity. A similar pattern was observed when imipramine (3.75 and 7.5 mg/kg IM) was administered repeatedly (2 injections/day/4 days). The failure of imipramine to decrease separation-induced vocalizations in our conditions suggests that the procedure would not be useful for testing potential antidepressants.

Animals↗
PubMed1984

Habituation of exploratory activity in mice: effects of combinations of piracetam and choline on memory processes.

The effects of various piracetam + choline combinations on an experimental model of memory were investigated. Mice were given two sessions in a simple photo-cell activity cage and the decrease in activity at the second session (habituation) served as an index of retention. Retention was facilitated by post-session administration of 2000 mg/kg piracetam IP and 50 mg/kg piracetam + 50 mg/kg choline IP. Similar injections of choline alone (10 to 200 mg/kg IP), piracetam alone (10 to 1000 mg/kg IP) or other combinations of piracetam and choline were without effect. These results, consistent with those reported elsewhere, suggest that piracetam can interact with choline to facilitate memory processes in mice.

Animals↗
PubMed1983

Neuropharmacological profile of MD 790501, a new benzamide derivative.

Using several classical screening procedures in different species MD 790501: (exo)-2,3 dimethoxy-N-[8-(phenylmethyl)-8-azabiocyclo [3.2.1]oct-3-yl] benzamide hydrochloride was shown to possess potent neuroleptic properties. The doses effective in the tests for neuroleptic activity were similar to or lower than those for heloperidol and clearly lower than those for bromopride, chlorpromazine, sulpiridie, sultopride and thioridazine. Compared with the reference compounds tested MD 790501 showed sedative, cataleptic and dyskinetic effects at doses relatively higher than those effective in tests for neuroleptic activity. MD 790501 possessed no noradrenolytic, anticholinergic, proconvulsant or anxiolytic activity. Its acute toxicity was in the same dose range as that of reference neuroleptics.

Animals↗
PubMed1982

Habituation of exploratory activity in mice: a screening test for memory enhancing drugs.

The habituation of exploratory activity was investigated as an experimental model of memory processes. Mice were given two sessions in a simple photo-cell activity cage and the decrease in activity at the second session (habituation) served as an index of retention. Retention decreased as the interval between sessions increased from 1 to 7 days. Retention was facilitated or impaired by post-session. IP injections of several drugs known respectively to improve [(+)-amphetamine, nicotine, physostigmine, strychnine] or impair (chlordiazepoxide, chlorpromazine, scopolamine) memory in other animal models. Memory facilitation or impairment only occurred if administration of the enhancing or impairing agent closely followed the first session, suggesting that the consolidation period was of limited duration. Post-session administration of presumably rewarding or noxious stimuli did not affect retention. Finally, retention was enhanced by several drugs which are used clinically for the treatment of memory disorders (bromocriptine, dihydroergotoxine, meclofenoxate, naftidrofuryl and piracetam). These results, consistent with classical learning data, suggest that habituation of exploratory activity in mice provides a simple but valid model of memory processes suitable for the screening of memory enhancing drugs.

Animals↗
PubMed1982

Antiapomorphine and locomotor effects of neuroleptics in rhesus monkeys.

Intramuscular injections of apomorphine (1 mg/kg) cause marked behavioral effects in rhesus monkeys including hyperactivity, repetitive stereotyped movements, chewing, tongue movements, licking, biting and vocalization. These effects occur within minutes of the injection and last 90-100 min. The antiapomorphine and locomotor depressant activity of chlorpromazine, haloperidol, MD 790501, sultopride and thioridazine, injected IM 1 hr before apomorphine, were assessed using a standardized rating procedure. All compounds antagonized the effects of apomorphine but differed in terms of potency and their relative effects on locomotor activity. The experimental compound MD 790501, a new benzamide derivative, was not only the most potent compound tested but, compared with its antagonism of apomorphine, caused the least marked depression of locomotor activity.

Animals↗
PubMed1982

Neuropharmacological profile of MD 780515, a new reversible inhibitor of type A monoamine oxidase.

Using several classical screening procedures, MD 780515, 3-[[4-[5-(methoxymethyl)-2-oxo-3-oxazolidinyl]phenoxy]methyl]- benzonitrile, was shown to possess potential antidepressant activity consistent with preferential and short-acting inhibition of type A monoamine oxidase. The doses effective in the tests for antidepressant activity were much lower than the lethal doses and were similar to or lower than those for reference drugs. MD 780515 showed some anti-convulsant action but had little effect on spontaneous or conditioned behaviour and was devoid of anticholinergic activity.

Animals↗
PubMed1981

Neuroleptic-induced acute dyskinesias in rhesus monkeys.

Rhesus monkeys, previously subjected to twice-weekly injections of various neuroleptics, subsequently respond to acute IM injections of haloperidol with marked bucco-lingual and whole body movement disturbances consisting of mouth opening, protrusion, retraction or curling of the tongue together with writhing movements of the neck, trunk and/or limbs. These phenomena, which closely resemble the acute dyskinetic or dystonic reactions described in patients at the beginning of neuroleptic treatment, were also observed after acute IM injections of other neuroleptics such as fluphenazine, metoclopramide, oxiperomide, sulpiride, sultopride and tiapride. No dyskinesias were observed after chlorpromazine, chlordiazepoxide, clozapine, RMI81582 or thioridazine at doses which otherwise had marked behavioural effects. The dyskinesias induced by haloperidol could be suppressed by prior treatment with the anti-cholinergic scopolamine. These observations, which correlate well with clinical findings, suggest that neuroleptic induced acute dyskinesias in the Rhesus monkey might be a useful model for predicting the liability of new anti-psychotics for inducing acute dyskinetic reactions in man.

Acute Disease↗
PubMed1979

Forced swimming in rats: hypothermia, immobility and the effects of imipramine.

Rats when forced to swim in a restricted space not only became immobile but showed marked hypothermia. The hypothermia was greater than that observed after reserpine or Ro 4-1284 and was not antagonized by imipramine at doses which significantly reduced immobility. Hypothermia induced by forced swimming can therefore be dissociated from the immobility occurring in these conditions and also from drug-induced hypothermia.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1979

Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity.

Rats were forced to swim in a restricted space will rapidly cease apparent attempts to escape and adopt a characteristic posture which we have termed "immobility". We show in previous experiments that immobility was reduced by a variety of antidepressant agents and thus suggested that the method could serve as a screening model for antidepressants. The present experiments showed that immobility was reduced by drugs which increase central dopaminergic and alpha-adrenergic activity but was less affected by drugs which act mainly on central serotonin. Conversely, immobility could be increased by drugs which diminish central catecholamine activity but not by drugs which inhibit central serotonin. It was concluded that immobility depended primarily on the activity of central catecholamines but that caution was required before ascribing immobility exclusively to activity within a single system.

Animals↗
PubMed1979

Animal model of depression.

A behavioural procedure is described which may provide an animal model for some aspects of human depression. Rats or mice when forced to swim in a restricted space will rapidly cease attempts to escape and become immobile. Immobility is reduced by many clinically effective antidepressant treatments suggesting that the immobile behaviour may reflect a state of lowered mood in the animal. If so the method could be useful as a simple experimental tool for research into the biology and therapeutics of depression.

Animals↗
PubMed1978

"Behavioural despair" in rats and mice: strain differences and the effects of imipramine.

Rats and mice when forced to swim in a restricted space will rapidly cease attempts to escape and become immobile. Previous experiments have shown that immobility was selectively reduced by antidepressant agents. The present experiments show that important differences exist between strains in both the amount of immobility observed and the effects of imipramine. Strain differences should therefore be taken into account in attempts to replicate results from one laboratory to another.

Animals↗