Premium
Effects of Two Convulsant β‐Carboline Derivatives, DMCM and β‐CCM, on Regional Neurotransmitter Amino Acid Levels and on In Vitro D‐[ 3 H]Aspartate Release in Rodents
Author(s) -
Chapman Astrid G.,
Cheetham Sharon C.,
Hart Geneen P.,
Meldrum Brian S.,
Westerberg Eva
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb03998.x
Subject(s) - chemistry , striatum , glutamate receptor , pharmacology , hippocampus , aminobutyric acid , medicine , endocrinology , receptor , biochemistry , dopamine , biology
Clonic seizures were induced in Swiss or DBA/2 mice by methyl‐6‐7‐dimethoxy‐4‐ethyl‐β‐carboline‐3‐carboxylate (DMCM), 0.048 mmol/kg i.p., or by methyl‐β‐carboline‐3‐carboxylate (β‐CCM), 0.044 mmol/kg i.p. Measurement of regional brain (cortex, hippocampus, striatum, and cerebellum) amino acid levels after 15 min of seizure activity showed increases in γ‐aminobutyric acid (GABA) (in all regions after β‐CCM, and in cortex and hippocampus after DMCM), and an increase in glycine in the striatum after β‐CCM. Aspartate levels fell (in cortex and hippocampus) after DMCM, but were unchanged in all regions after β‐CCM. Glutamate levels fell in cortex after β‐CCM and in striatum after DMCM. Pretreatment with the excitatory amino acid receptor antagonist, 2‐amino‐7‐phosphonoheptanoic acid, 0.5 mmol/kg i.p., 45 min prior to the β‐carboline, significantly increased the ED 50 for DMCM‐induced clonic seizures (4.68 μmol/kg vs. 9.39 μmol/kg). Similar pretreatment did not significantly alter the ED 50 for β‐CCM (4.22 μmol/kg vs. 6.6 μmol/kg). Pretreatment with 2‐amino‐7‐phosphonoheptanoic acid, 1.0 mmol/kg, blocked the increase in GABA content produced by DMCM but not the fall in cortical aspartate content. Potassium‐induced release of preloaded D‐[ 3 H]aspartate from rat cortical or hippocampal minislices was enhanced in the presence of DMCM (100 μ M ). In contrast, stimulated release of D‐[ 3 H]aspartate (from cortex or hippocampus) was not altered in the presence of β‐CCM (100 μ M ). Although DMCM and β‐CCM are both considered to induce convulsion by acting at the GABA‐benzodiazepine receptor complex, the convulsions differ in several pharmacological and biochemical respects. It is suggested that enhanced release of excitatory amino acid neurotransmitters plays a more important role in seizures induced by DMCM.