ergoline and Epilepsies--Myoclonic

Previous studies have shown that mice bearing a targeted disruption of the 5-HT2C receptor gene exhibit an epilepsy syndrome associated with sporadic spontaneous seizures that occasionally result in death. In this study, we have defined the seizure susceptibility profiles of these 5-HT2C receptor mutant mice backcrossed onto a C57BL/6 background. Wild-type and mutant animals were either electrically kindled from the olfactory bulb, exposed to corneal electroshock, or tested with the chemoconvulsant, flurothyl. In all paradigms, mice lacking the 5-HT2C receptor were significantly more seizure susceptible than wild-type controls. Results indicate that mutants have lower focal seizure thresholds, increased focal seizure excitability, and facilitated propagation within the forebrain seizure system. Mutants also exhibit lower generalized seizure thresholds for the expression of both generalized clonic and generalized tonic seizures. Importantly, the 5-HT receptor antagonist, mesulergine (2 or 4 mg/kg), administered prior to electroshock testing, recapitulated the mutant phenotype in wild-type mice. Together, these data strongly implicate a role for serotonin and 5-HT2C receptors in the modulation of neuronal network excitability and seizure propagation globally, throughout the CNS.

Topics: Animals; Behavior, Animal; Brain Chemistry; Convulsants; Cornea; Disease Susceptibility; Dopamine Agonists; Electroshock; Epilepsies, Myoclonic; Epilepsy; Ergolines; Flurothyl; Kindling, Neurologic; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Knockout; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin

When human divers and experimental animals are exposed to an increasing environmental pressure, they develop the high pressure neurological syndrome (HPNS) characterized by electroencephalographic changes and sleep and behavioral disturbances. In rats, behavioral disturbances essentially include hyperlocomotor activity (HLA), tremor and myoclonia. Moreover, HLA has recently been demonstrated to be linked to a pressure-induced striatal increase of dopamine (DA). In these experiments, it was proposed to investigate in rats, at the behavioral level, the role of DA receptors in the occurrence of the pressure-induced DA disturbances. DA receptor agonists were found to induce no significant changes in the development of HLA, tremor, and myoclonia. Alternatively, HLA was found to be dramatically antagonized by the use of DA receptor antagonists (SCH 23390, sulpiride, and haloperidol), while tremor and myoclonia only decreased in SCH 23390 experiments.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Apomorphine; Atmospheric Pressure; Behavior, Animal; Dopamine Agents; Epilepsies, Myoclonic; Ergolines; Haloperidol; High Pressure Neurological Syndrome; Injections, Intraventricular; Male; Motor Activity; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Sulpiride; Tremor

Two patients with a diagnosis of olivo-ponto-cerebellar atrophy developed cortical reflex myoclonus to visual (flash) and somaesthetic stimuli. Oral treatment with levodopacarbidopa (1000/100 mg) or subcutaneous administration of apomorphine (1 mg) abolished the visually-triggered myoclonus, without modifying reflex myoclonus to electrical or tactile stimulation. Intravenous administration of lisuride (0.1 mg) produced a marked reduction in both types of reflex myoclonus. These results indicate a selective inhibitory effect of dopamine agonist drugs on visual reflex myoclonus of cortical origin.

Topics: Aged; Apomorphine; Atrophy; Carbidopa; Cerebellum; Drug Therapy, Combination; Electromyography; Epilepsies, Myoclonic; Ergolines; Evoked Potentials, Somatosensory; Evoked Potentials, Visual; Female; Humans; Levodopa; Lisuride; Olivary Nucleus; Photic Stimulation; Pons; Reflex; Visual Cortex

Six patients with myoclonus were given 0.1-0.15 mg lisuride i.v. All patients had stimulus-sensitive myoclonus and an increased size of somatosensory evoked potentials, and in three there was electrophysiological evidence of a cortical event time-locked to the jerks. All subjects showed a considerable diminution of spontaneous, action- and stimulus-evoked jerking. Lisuride has potent central dopaminergic and serotonergic actions. Administration of the dopamine agonists levodopa or apomorphine had no effect on myoclonic jerking in any of the six patients. Detailed pharmacological analysis of the myoclonus in one patient showed that levodopa, apomorphine, and haloperidol had no effect, and that haloperidol did not prevent the therapeutic action of lisuride. 5-Hydroxytryptophan abolished the myoclonus, and methysergide prevented the beneficial effect of lisuride, although it did not alter spontaneous myoclonus. These observations suggest that lisuride improves some types of reflex, stimulus-sensitive cortical myoclonus by a serotonin agonist action.

Topics: Adult; Aged; Atrophy; Cerebral Cortex; Electroencephalography; Epilepsies, Myoclonic; Epilepsy, Post-Traumatic; Ergolines; Evoked Potentials, Somatosensory; Female; Humans; Lisuride; Male; Middle Aged; Reflex; Somatosensory Cortex