strychnine and glutamic-acid-diethyl-ester

Bilateral inferior olive lesions, produced by systemic administration of the neurotoxin 3-acetylpyridine (3AP) produce a proconvulsant state specific for strychnine-induced seizures and myoclonus. We have proposed that these phenomena are mediated through increased excitation of cerebellar Purkinje cells, through activation of glutamate receptors, in response to climbing fiber deafferentation. An increase in quisqualic acid (QA)-displaceable [3H]AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid] binding in cerebella from inferior olive-lesioned rats was observed, but no difference in [3H]AMPA binding displaced by glutamate, kainic acid (KA) or glutamate diethylester (GDEE) was seen. The excitatory amino acid antagonists GDEE and MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10 imine] were tested as anticonvulsants for strychnine-induced seizures in 3AP inferior olive-lesioned and control rats. Neither drug effected seizures in control rats, however, both GDEE and MK-801 produced a leftward shift in the strychnine-seizure dose-response curve in 3AP inferior olive-lesioned rats. GDEE also inhibited strychnine-induced myoclonus in the lesioned group, while MK-801 had no effect on myoclonus. The decreased threshold for strychnine-induced seizures and myoclonus in the 3AP-inferior olive-lesioned rats may be due to an increase in glutamate receptors as suggested by the [3H]AMPA binding data.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Anticonvulsants; Dizocilpine Maleate; Epilepsies, Myoclonic; Glutamates; Ibotenic Acid; Male; Olivary Nucleus; Pyridines; Quisqualic Acid; Rats; Rats, Inbred Strains; Seizures; Strychnine; Tritium

Topics: Animals; Excitatory Amino Acid Antagonists; Female; Glutamates; Pentylenetetrazole; Rats; Rats, Inbred Strains; Seizures; Strychnine

Seven antagonists of putative neurotransmitters were applied to bulbar respiratory neurons and, for comparison, also to unspecific cells. The antagonists exerted distinct effects when released alone, permitting to draw conclusions about receptor properties of the various cell types. With strychnine, specific antagonist of glycine, excitation prevailed in EI, I and E neurons. With bicuculline, specific antagonist of GABA, excitation preponderated in EI and E cells. About half of the unspecific neurons were activated and the remainder were unresponsive. GDEE (glutamatediethylester), antagonist of glutamate, excited part of the IE neurons and inhibited part of the E units, while the remainder of both types as well as 2 EI cells tested were not affected. With flupentixol, antagonist of dopamine, excitation prevailed in I neurons. About half of the IE and E units remained unaffected, while in the remainder E cells inhibition preponderated over excitation. With yohimbine, an alpha-adrenoceptor blocker, inhibition prevailed in E units. The two EI as well as the majority of the I neurons remained unaffected, with two cells of the latter type being activated. Propranolol, a beta-adrenoceptor blocker, inhibited about half of the E neurons, while the remainder as well as most IE and the 2 EI cells tested were not affected. Cyproheptadine, an antagonist of 5-HT, excited most E neurons. As concerns NE-receptors, those of the alpha-type might be involved in activation of part of the E cells only, whereas all other NE effects (inhibition or activation) are mediated by CNS-specific receptors different from the alpha- and beta-type. 5-HT effects apparently are mediated by two different receptor types.

Topics: Alkaloids; Animals; Bicuculline; Cyproheptadine; Flupenthixol; Glutamates; Iontophoresis; Neurons; Neurotransmitter Agents; Propranolol; Rabbits; Respiratory System; Secologanin Tryptamine Alkaloids; Strychnine