Posttreatment with group II metabotropic glutamate receptor agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate is only weakly effective on seizures in immature rats.

Abstract

The present study has examined the anticonvulsant and neuroprotective effect of 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), a selective agonist for group II metabotropic glutamate receptors (mGluRs) when given 10-15 min after the onset of seizures induced in 12-day-old rats by bilateral icv infusion of DL-homocysteic acid (DL-HCA, 600 nmol/side). For biochemical analyses, rat pups were sacrificed during generalized clonic-tonic seizures, approximately 45-50 min after infusion of DL-HCA. Comparable time intervals were used for sacrificing the animals which received 2R,4R-APDC (0.05 nmol/side) or saline. The severity of seizures was influenced only slightly when the agonist was given after the onset of seizures, as evaluated both from the behavioral symptoms and from EEG recordings. A tendency to lower number and a shorter duration of seizures was outlined in animals posttreated with 2R,4R-APDC, but the differences did not reach the level of statistical significance. Cortical energy metabolite changes which normally accompany seizures in immature rats (large decrease of glucose and glycogen and a marked rise of lactate) were ameliorated only partially. The neuroprotective effect of 2R,4R-APDC was evaluated after 24 h and 6 days of survival following DL-HCA-induced seizures. Massive neuronal degeneration in many brain regions, mainly in the hippocampus and thalamus, following infusion of DL-HCA alone was only partially attenuated after 2R,4R-APDC posttreatment. The present findings clearly indicate that both anticonvulsant and neuroprotective effect of 2R,4R-APDC against DL-HCA-induced seizures is substantially diminished when the agonist is given after the onset of seizures as compared with its efficacy after the pretreatment (Exp. Neurol.192, 420-436, 2005).

• Authors: Jaroslava Folbergrová, Rastislav Druga, Grygoriy Tsenov, Renata Haugvicová, Jakub Otáhal
• Journal: Brain research (Brain Res) Vol. 1273 Pg. 144-54 (Jun 01 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19341715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-aminopyrrolidine-2,4-dicarboxylic acid
• Convulsants
• Excitatory Amino Acid Agonists
• Neuroprotective Agents
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor 2
• Homocysteine
• homocysteic acid
• Proline

Topics

• Aging (metabolism)
• Animals
• Brain (drug effects, growth & development, metabolism)
• Convulsants (pharmacology)
• Cytoprotection (drug effects, physiology)
• Drug Administration Schedule
• Drug Interactions (physiology)
• Epilepsy (drug therapy, metabolism, physiopathology)
• Excitatory Amino Acid Agonists (therapeutic use)
• Hippocampus (drug effects, growth & development, metabolism)
• Homocysteine (analogs & derivatives, pharmacology)
• Male
• Nerve Degeneration (chemically induced, physiopathology, prevention & control)
• Neuroprotective Agents (therapeutic use)
• Proline (analogs & derivatives, therapeutic use)
• Rats
• Rats, Wistar
• Receptors, Metabotropic Glutamate (agonists, metabolism)
• Thalamus (drug effects, growth & development, metabolism)
• Treatment Outcome