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O Kofman

Publications and source records attributed to O Kofman.

49 records · Page 3Linked to original sources
PubMed1990

Role of inositol-1-phosphatase inhibition in the mechanism of action of lithium.

Li inhibition of noradrenergic adenylate cyclase may be due to inhibition by Li of agonist-induced increases in GTP binding to G-protein. Such inhibition by Li of G-protein function could have effects on phosphatidyl-inositol-mediated second messenger systems as well as on cyclic AMP-mediated systems. However, Sherman, Berridge and others have proposed that Li affects phosphatidylinositol metabolism by inhibiting inositol-1-phosphatase. We recently have been able to measure inositol-1-phosphatase in human red blood cells. Preliminary data on patients treated with Li compared with controls suggests that the enzyme is indeed inhibited in vivo in patients undergoing Li treatment. However, a series of experiments in rats on addition of inositol to Li treatment did not find that inositol could reverse Li effects. Chronic oral high dose inositol does not reverse Li-induced polyuria (measured by polydipsia), Li-induced weight loss or Li-induced depression of exploratory behavior. These results suggest that Li inhibition of inositol-1-phosphatase indeed occurs in vivo. However, the physiological significance of inositol-1-phosphatase inhibition is not yet established.

Animals↗
PubMed1988

Cholinergic antagonists in ventral tegmentum elevate thresholds for lateral hypothalamic and brainstem self-stimulation.

Frequency thresholds for lateral hypothalamic self-stimulation are elevated following microinjections of atropine into ventral tegmentum (73). Many self-stimulation sites in brainstem are situated near cholinergic cell groups and axons, and ventral tegmentum receives cholinergic afferents terminals. To test the hypothesis that ventral tegmental muscarinic receptors are involved in lateral hypothalamic and brainstem self-stimulation, stimulating electrodes were placed in lateral hypothalamus and dorsal tegmentum near the midbrain-pons border, and cannulae were implanted in ventral tegmentum. Microgram injections of muscarinic antagonists, atropine or scopolamine, or a choline uptake blocker, hemicholinium-3, elevated frequency thresholds for both self-stimulation sites in a dose-dependent and time-dependent fashion. In addition, summation and collision between the two self-stimulation sites was tested using paired-pulse methods (53). Summation ranged from 31 to 87% (i.e., 24 to 47% reductions in frequency threshold were observed at long intrapair intervals), but no collision-like effects were observed at short intrapair intervals. The ventral tegmentum is a likely site for the convergence of dorsal tegmental and lateral hypothalamic self-stimulation pathways.

Animals↗
PubMed1985

Cholinergic involvement in lateral hypothalamic rewarding brain stimulation.

Rats were implanted with stimulating electrodes in the lateral hypothalamus, and cannulae for chemical injections in the ventral tegmentum. Injections of atropine, a muscarinic antagonist, increased thresholds for self-stimulation in a dose-dependent fashion, without slowing bar pressing rates. Thresholds increased less for a self-stimulation site contralateral to the atropine injection. In a conditioned place preference test, the rats preferred compartments in which they received carbachol, a cholinergic agonist. Muscarinic receptors in ventral tegmentum therefore seem critical for medial forebrain bundle (MFB) reward. The possible cholinergic cells of origin are discussed.

Animals↗
PubMed1983

Regular and lasting neocortical spiking produced by systemic administration of a steroid derivative in the rat.

The hypothesis was tested that sedation and stereotyped behaviour, developing in rats after the administration of the steroid derivative with gamma-aminobutyric acid (GABA) antagonistic properties, R 5135, are of an epileptiform nature. Electroencephalographic (EEG) and visual evoked potentials (VEP) were recorded and behaviour was observed over not less than 5-7 hr after subconvulsive doses of R 5135. Doses of 2-4 mg/kg of the compound produced quasi-rhythmic spikes resembling experimental focal epileptic discharges in all rats. This epileptiform activity was accompanied by behavioural sedation and somnolence, followed by a build-up of stereotyped behaviour and sporadic episodes of epileptiform motor activity, developing 1-2 hr after injection. The secondary components (SNW) of the visual evoked potentials were suppressed by R 5135 and the primary potential (N1) facilitated, virtually reducing the visual evoked potential to the form of an evoked spike. Pretreatment with the anticonvulsant GABAergic drugs gamma-acetylenic GABA (GAG) (100 mg/kg), sodium valproate (VPA) (400 mg/kg) and diazepam (5 mg/kg) suppressed the motor components of seizure activity, producing severe ataxia, but not the electrographic manifestation of seizure activity. Neither gamma-acetylenic GABA nor valproate significantly altered the latency to onset of spiking, although all three drugs did significantly reduce the frequency of discharges. Diazepam was the only anticonvulsant tested which completely suppressed spike activity in 3 of 5 rats. Moreover, R 5135 was found to antagonize diazepam, but not valproate induced suppression of secondary components of the visual evoked potential, suggesting that diazepam and R 5135 may compete for the same receptor.

Action Potentials↗
PubMed1982

Unilateral Versus bilateral electroconvulsive shock in albino rats: comparison of behavioral symptomatology and neocortical reactivity changes.

Electrophysiological studies have shown asymmetric brain reactivity in schizophrenia, supporting the hypothesis of left hemisphere hyperarousal in this disease. It may be assumed, therefore, that neuroleptic treatment restores hemispheric balance in schizophrenic patients by selectively suppressing the hyperactive left hemisphere. This hypothesis was tested in the present study, which compared bilaterally recorded visual evoked potentials (VEP) in 9 nonmedicated patients and 29 schizophrenics treated with various neuroleptic drugs, as well as in 34 normal controls. In medicated patients later VEP components showed enhancement over the right hemisphere as a function of the overall dose (chlorpromazine equivalent) of neuroleptics. Reversed asymmetry was seen in drug-free patients. In view of this result, some amendments of the concept of left hemisphere hyperactivity in schizophrenia are proposed.

Animals↗
PubMed1981

Pharmacologic analysis of the postictal immobility syndrome in the rat.

Postictal immobility (IP) following chemically (pictrotoxin, metrazol) and electrically-induced (maximal electroshock, MES) convulsions has behavioral features close to neuroleptic-type catalepsy. EEG, monitored postictally, showed that catalepsy is accompanied by a variety of EEG patterns. Cataleptic behavior extended beyond the period of "postictal EEG depression". During PI rats had vivid righting and corneal reflexes. Like haloperidol-pretreated rats they were able to maintain uncomfortable postures on the vertical grid or horizontal bar; although signs of rigidity were noticed, the rats would fail to remain self-supporting when placed across metal bookends ("bridge" test). All rats reacted to the tail-pinch immediately when the seizure would halt. However, 10-15 min later when PI was minimal or not detectable, animals became totally unresponsive to pressure applied to the tail ("delayed analgesia"). Examination of VEP recovery after MES showed that the secondary slow negativity and sensory after discharge were well developed irrespective of the score of the tail-pinch test. Pharmacological profile of PI suggests that the endogenous opiate system might contribute to this syndrome. Similar to morphine-induced catalepsy/catatonia: (1) PI is insensitive to atropine and scopolamine; (2) neither haloperidol nor alpha-methyl-p-tyrosine was able to potentiate it; (3) PI is reduced by apomorphine, naloxone, and physostigmine. Also, drugs acting via GABA system (gamma-vinyl GABA, diazepam, sodium valproate) reduce PI intensity. It is hypothesized that PI system (1) is controlled by GABA carrying fibers and (2) uses neuropeptide with neuroleptic properties.

Animals↗
PubMed1981

Convulsant-specific architecture of the postictal behavior syndrome in the rat.

The postictal immobility syndrome was examined in five experimental grand mal epilepsy models in an attempt to analyze separately the behavioral and underlying neurochemical aspects of the rigid-catatonic and flaccid-cataleptic states. Catalepsy and analgesia were found in varying degrees after maximal electroshock (MES), metrazol, picrotoxin, and Ro 5-3663 activated seizures. Signs of rigidity were noticed after the MES and picrotoxin seizures. Kindled seizures were followed by explosive behavior without signs of rigidity, catalepsy, and analgesia. Naloxone reduced the duration but not the score (intensity) of catalepsy and failed to selectively antagonize analgesia. The relative representation of the tonic stage of convulsions seemed to be the major determinant of the development of catatonic-cataleptic symptomatology. It is suggested that more than a single neurotransmitter system is involved in the postictal immobility syndrome and each epilepsy model has its unique neurochemical profile.

Animals↗
PubMed1978

Sexual function and affect in parkinsonian men treated with L-dopa.

Using psychiatric interviews, sexual and affect rating scales, hormonal studies, and neurologic assessment, the authors assessed the effect of L-dopa treatment on men with Parkinson's disease. Patients demonstrated variable affect changes. Approximately one-half of the patients reported an increased sexual interest that was not related to improvement in locomotor function. Hormonal factors appeared to be involved. The findings suggest that male parkinsonian patients who possess an intact hypothalamic-pituitary-gonadal axis experience increased sexual function related to L-dopa treatment.

Affect↗
PubMed1971

Treatment of Parkinson's disease with L-dopa: a current appraisal.

Interest in l-dopa therapy for Parkinson's disease has been considerably enhanced since the recent release of this drug to all medical practitioners. Our experience in the use of l-dopa in 83 patients who have been treated during the past 22 months is presented to provide a practical approach to the administration of l-dopa. Many parkinsonian patients can be treated advantageously on an outpatient basis without the need for initial hospitalization. Some of the common side effects of l-dopa administration can be averted or controlled by a cautious and slow build-up to the optimal dosage level. In the majority (78%) of parkinsonian patients who had been carefully selected for treatment the drug had a beneficial effect on akinesia and rigidity. In the remainder, therapy had to be discontinued because of undesirable side effects or a limited response.

Adolescent↗
PubMedDate not supplied

Lack of effect of ECS on rat brain inositol monophosphatase activity and inositol levels and of i.c.v. inositol on ictal and post-ictal length.

Lithium (Li) has often been compared to ECT in therapeutic spectrum and mechanism. Inhibition of inositol monophosphatase and reduction of brain inositol are major mechanisms of Li action. Many Li effects in animals and humans are reversible by inositol. We therefore studied interactions of ECS and inositol. ECS in rats did not reduce brain inositol monophosphatase activity or brain inositol levels. Intracerebroventricular injection of 10 mg inositol, a dose that reverses Li effects, had no effect on seizure length or post-ictal length.

Animals↗
PubMedDate not supplied

Epileptogenic activity in the amygdala is not affected by the amidine steroid, R 5135.

The synthetic steroid amidine 3-alpha-hydroxy-16-imino-5-beta-17aza androstan-11-one (R 5135) is known to elicit long-lasting spiking in the cortex in the presence of neocortical damage. R 5135 administered to amygdaloid-kindled and naive rats resulted in regular, high-amplitude spiking in the cortex but only occasionally elicited small-amplitude spikes in the amygdala (AMY) and hippocampus (HPC). Interictal spikes from the AMY of kindled rats were not synchronized with cortical spikes induced by the steroid. Given that R 5135 is known to be a GABAA receptor antagonist, these findings suggest that GABAA receptors in AMY and HPC may have lower affinity for 3 alpha-hydroxysteroids.

Amygdala↗