[The atypical neuroleptic concept].

Atypical neuroleptics can be defined as dopamine (DA) receptor blockers which differ from typical neuroleptics in that they have a markedly lower or absent propensity for the induction of parkinsonian side effects of tardive dyskinesias. Some of them, but not all, are also more effective in treating schizophrenic patients, i.e.

[Transcerebral electrostimulation in hypnotic drug withdrawal].

This preliminary study attempted to test the efficacy of electrosleep therapy on hypnotic drug withdrawal. Among 89 outpatients complaining of chronic insomnia and receiving a heavy hypnotic drug treatment, an efficient withdrawal associated with a marked improvement of self-reported sleep was observed in 78% of cases, especially when insomnia was not related to medical aetiologies or to major psychiatric disorders. These results suggest further controlled studies to determine the magnitude of the placebo component in the effect observed.

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.

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.

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).

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.

Aortic occlusion by a balloon catheter: a method to induce hind limb rigidity in rats.

Post-ischaemic spinal extensor or flexor rigidity can be induced in different species by clamping or ligature of the descending aorta after thoracotomy or laparotomy. A similar motor deficit can also be induced by an intraluminal aortic occlusion produced by inflation of a balloon attached to the tip of a catheter inserted via the femoral artery. This method is easy to perform and avoids all the possible complications of thoracotomy or laparotomy.

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.

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.

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.

Animal pharmacology of oxapadol (MD 720111), a new non-narcotic analgesic.

Oxapadol is a non-narcotic analgesic with an unusual chemical structure. It possesses analgesic activity in 4 species similar to that of other non-narcotic reference analgesics. It also shows antipyretic and antiinflammatory effects and in the analgesic dose range is devoid of undesirable neurological, gastro-intestinal and cardiovascular side-effects.

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.

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.

"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.

Behavioural despair in rats: a new model sensitive to antidepressant treatments.

Rats when forced to swim in a cylinder from which they cannot escape will, after an initial period of vigorous activity, adopt a characteristic immobile posture which can be readily identified. Immobility was reduced by various clinically effective antidepressant drugs at doses which otherwise decreased spontaneous motor activity in an open field. Antidepressants could thus be distinguished from psychostimulants which decreased immobility at doses which increased general activity.

Behavioral despair in mice: a primary screening test for antidepressants.

A depressed state can be induced in mice by forcing them to swim in a narrow cylinder from which they cannot escape. After a brief period of vigorous activity the mice adopt a characteristic immobile posture which is readily identifiable. Immobility was reduced by tricyclic antidepressants, monoamine oxidase inhibitors and atypical antidepressants, as well as by electroconvulsive shock.

[Alerting effect of vincamine in rats (author's transl)].

The alerting effect of vincamine, an indole alkaloid of Vinca minor, has been demonstrated using three electropharmacological tests: 1) the sleep-wakefulness cycle of freely moving rats implanted with cortical electrodes, 2) the sleep induced by 200 mg/kg i.v. sodium 4-hydroxy-butyrate (GHB) in the curarized rat, 3) the duration of spindle activity in the E.

Drugs and PGO waves in the lateral geniculate body of the curarized cat. III. PGO wave activity and brain catecholamines.

The possible implication of central catecholamines in the phasic phenomenon of ponto-geniculo-occipital (PGO) waves was investigated using PGO waves induced by the benzoquinolizine derivative, Ro 4-1284 (=PGO(1284), and the inhibitor of tryptophan hydroxylase, p-chlorophenylalanine (=PGO(PCPA); they were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in a previous report. The effect on PGO(1284) and PGO(PCPA) of various drugs interacting with the different steps of catecholaminergic transmission was studie. Injections of noradrenaline (NA) and of dopamine (DA) into the lateral brain ventricle tended to decrease the density of PGO(1284).

Drugs and PGO waves in the lateral geniculate body of the curarized cat. II. PGO wave activity and brain 5-hydroxytryptamine.

Ponto-geniculo-occipital (PCO) waves induced either by the benzoquinolizine derivative, Ro 4-1284 (=PGO(CPA), were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in the preceding communication. The effect of various drugs interacting with central 5-hydroxytryptaminergic mechanisms on the density (number hr(-1) or number 0.5 hr(-1) of PGO waves was investigated.

Drugs and PGO waves in the lateral geniculate body of the curarized cat. IV. The effects of acetylcholine, GABA and benzodiazepines on PGO wave activity.

The possible involvement of cholinergic mechanisms and of GABA in the modulation and generation of ponto-geniculo-occipital (PGO) waves was studied using PGO waves induced by the benzoquinolizine derivative, Ro 4-1284 ( =PGO(1284)), and by p-chlorophenylalanine (=PGO(PCPA)), and continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats. Atropine had no significant effect on PGO(1284) but markedly depressed the density of PGO(PCPA) this effect of atropine was absent when the synthesis of noradrenaline (NA) was inhibited in addition to that of 5-hydroxytryptamine (5-HT). Arecoline and eserine at a low dose increased the density of PGO(PCPA).

Drugs and PGO waves in the lateral geniculate body of the curarized cat. I. PGO wave activity induced by Ro 43284 and by p-chlorophenylalanine (PCPA) as a basis for neuropharmacological studies.

Depletion, either predominantly of brain noradrenaline (NA) or preferentially of brain 5-hydroxytryptamine (5-HI), was achieved in cats by a single i.p. dose of 20 mg kg(-1) of Ro 4-1284, a benzoquinolizine derivative reducing the storage capacity of monoamine neurones, or by two i.

Drugs and PGO waves in the lateral geniculate body of the curarized cat. V. Miscellaneous compounds. Synopsis of the role of central neurotransmitters on PGO wave activity.

In the last part of this series we have studied the effects of various drugs on ponto-geniculo-occipital (PGO) waves induced by the benzoquinolizine derivative, Ro 4-1284 (PGO(1284)), and by the inhibitor of trypotophan hydroxylase, p-chlorophenylalanine (PGO(PCPA)), and continuously recorder and counted in the lateral geniculate bodies (LGB) of unanaesthetized and immobilizedcats. The major aim of this study was to test the specificity of drug-induced alterations of the PGO wave activity suggested by the previous investigations. Hypnotics-sedatives of different classes had no significant effects in doses that did not markedly alter the electrical background activity in the LGB.

Interaction of psychotropic agents with central neurotransmitters as revealed by their effects on PGO waves in the cat.

One of the phasic phenomena of REM (rapid eye movement) sleep, the ponto-geniculo-occipital (PGO) waves, are induced in cats by either depleting brain monoamines with the benzoquinolizine derivative Ro 4-1284 or inhibiting the synthesis of 5-hydroxy-tryptamine (5-HT) by p-chlorophenylalanine (PCPA). The effects of the most important psychotropic agents on PGO1284 and PGOPCPA are reported and explained by their interaction with one or more of the 4 neurotransmitters known so far to be involved in the regulation of the PGO wave generation in the pontine reticular formation. Tricyclic antidepressants depress PGO waves by inhibiting the neuronal uptake of norepinephrine (NE) and/or 5-HT.