Stimulus-sensitive myoclonus of the baboon Papio papio: Pharmacological studies reveal interactions between benzodiazepines and the central cholinergic system

Rektor, Ivan; Bryère, Philippe; Silva-Barrat, C.; Ménini, C

doi:10.1016/0014-4886(86)90021-x

Cited by 11 publications

(1 citation statement)

References 34 publications

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“…Furthermore, these neurons are cholinoceptive (33). Thus, for type B myoclonus, where a facilitatory effect of atropine has been reported (20,21), a blockade of the brainstem excitatory drive to glycinergic spinal interneurons would be the basis for the appearance of myoclonic activity.…”

Section: Physiopathological Considerationsmentioning

confidence: 97%

Myoclonus in Papio papio

Brailowsky¹

1991

Movement Disorders

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The baboon Papio papio has been extensively used over the last 25 years for studying different aspects of brain pathology, but most of all, epilepsy. Indeed, since the original description by the Killams and Naquet (1) of the occurrence of a syndrome of natural photosensitivity in baboons originating from the Casamance region in Senegal, this animal has been extremely useful for the analysis of the pathophysiological mechanisms involved in generalized epilepsy from cortical origin and for the preclinical evaluation of potentially useful anticonvuisant drugs. Furthermore, since the fortuitous finding of a nonepileptic spontaneous myoclonus (2), this animal has become also a model for the study of myoclonic syndromes.In this paper, we will summarize the current knowledge on the three types of myoclonus found in Papio papio, of both epileptic and nonepileptic origin. We will define myoclonus as a brief and involuntary contraction of one or several muscle groups (3). MYOCLONUS TYPE A (EPILEPSY-RELATED) Clinical ManifestationsIn predisposed baboons, intermittent light stimulation (ILS) at -25 Hz induces clinical manifestations of generalized epilepsy-bilateral myoclonus that, in order of appearance and of photosensitivity, has been classified in four stages: stage 1 = myoclonus of the eyelids; 2 = myoclonus of eyelids, face and head muscles; 3 = generalization to the trunk and proximal limb muscles (at any of these stages, myoclonus will stop at the cessation of ILS); stage ILS (4).The photosensitive syndrome varies with age, gender, and geographical distribution: monkeys younger than 6 months are not photosensitive and those between 9 months and 4 years of age are more reactive to light than older animals. Females are more photosensitive than males. Lastly, the animals originating from the Casamance region are more often photosensitive (-60% of them) then baboons captured in other regions of Senegal, where this figure descends to 6 2 0 % (5). Besides a maturational factor, no anatomical or histological variations have yet been found to explain these differences in epileptic predisposition. Genetic factors might be involved. Electrographic ManifestationsThe electrographic manifestations of photosensitive epilepsy have been studied in detail. The principal sign of the EEG response to light is the appearance of paroxysmal discharges (spikes, polyspikes, and spike and waves) localized to the frontocentral regions of the cortex. These paroxysmal discharges (PD) are bilateral, symmetric, and synchronous over both hemispheres, although recent evidence obtained in baboons with section of the corpus callosum indicate that each hemisphere can independently generate PD during ILS (6).'The ILS-induced PD have a precise and constant temporal association with myoclonic activity. The surface-positive spike is followed by muscle activation: at 4 ms in the orbicularis oculi, 7 ms in the masseter, 8 ms in the biceps, and 24 ms for the paravertebral muscles (7) (Fig. 1).Recordings from cortical unit activity have shown that areas 4 a...

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Section: Physiopathological Considerationsmentioning

confidence: 97%

Myoclonus in Papio papio

Brailowsky¹

1991

Movement Disorders

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Pharmacology of Cl‐966: A potent GABA uptake inhibitor, in vitro and in experimental animals

Taylor¹,

Vartanian²,

Schwarz³

et al. 1990

Drug Development Research

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Pharmacology of Cl-966: A potent GABA uptake inhibitor, in vitro and in experimental animals. Drug Dev. Res. 21 :195-215, 1990.Experiments were performed to assess the pharmacology of a novel inhibitor of GABA uptake, (21-966 ([1-[2-[bis 4-(trifluoromethyl)phenyl]methoxy]ethyl]-l,2,5,6-tetrahydro-3-pyridinecarboxylic acid, HCI salt; the molecular weight of the free acid is 473.8). Cl-966 potently inhibits tritiated GABA uptake into rat hippocampal slices in vitro (lC,o = 304 nM). It has no appreciable effect on the uptake of other neurotransmitters tested (aspartate, dopamine, norepinephrine, serotonin) and has low activity in a broad range of neurotransmitter receptor binding assays. When given orally to mice, Cl-966 prevents tonic extensor seizures from low-intensity electroshock and prevents pentylenetetrazole-induced clonic seizures ( ED, , = 0.4-1 .O mg/kg). In addition, the hippocampal afterdischarge threshold in kindled rats is increased markedly ( ED, , = 2.6 mg/kg p.0.). Despite anticonvulsant effects, higher doses of (21-966 reduce the intravenous dose of pentylenetetrazole needed to produce clonus in mice. In mice, rats, dogs, and monkeys, Cl-966 interferes with normal behavior, causing ataxia, reduced responsiveness and myoclonus. In the hippocampus of anesthetized rats, (3-966 increases inhibition measured electrophysiologically. Overflow of endogenous GABA in the striatum (measured with in vivo microdialysis) was also increased. All of these observed effects with Cl-966 may be explained by its inhibitory effect on GABA uptake.

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Influence of cholinergic system on myoclonus in myoclonic epilepsies

et al. 1992

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The effect of two drugs upon multifocal myoclonic jerks was evaluated. The drugs influence the central cholinergic system in opposite ways. Eight patients with progressive and nonprogressive myoclonic epilepsy were tested. The single blind test was used. The number of myoclonic jerks after intravenous physostigmine (mean dose 0.02 mg/kg) and that after atropine (0.04 mg/kg) was compared to number of myoclonic jerks in the drug-free periods and with placebo. Placebo was without an effect. Physostigmine slightly increased the number of jerks. Atropine decreased the number significantly. In most patients the results were not striking. It is suggested that the cholinergic system may participate in the physiopathology of the studied myoclonus in a rather indirect, perhaps modulating way.

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Stimulus-sensitive myoclonus of the baboon Papio papio: Pharmacological studies reveal interactions between benzodiazepines and the central cholinergic system

Cited by 11 publications

References 34 publications

Myoclonus in Papio papio

Myoclonus in Papio papio

Pharmacology of Cl‐966: A potent GABA uptake inhibitor, in vitro and in experimental animals

Influence of cholinergic system on myoclonus in myoclonic epilepsies

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