Related Experiment Video
Updated: Aug 3, 2026
Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
Cortical epileptic afterdischarges in immature rats are differently influenced by NMDA receptor antagonists
Romana Slamberová1, Pavel Mares
1Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, CZ-142 20 Prague 4, Czech Republic.
Abstract:
Epileptic afterdischarges elicited by stimulation of sensorimotor cortex were chosen to test anticonvulsant effects of NMDA receptor antagonists in developing rats (12, 18 and 25 days old) with implanted electrodes. Afterdischarges were elicited four times with 10-min intervals in the experiments with dizocilpine and 20 min with the other two drugs. Dizocilpine (0.5 or 1 mg/kg), CGP 40116 (0.1, 0.5 or 1 mg/kg) or 2-amino-7-phosphonoheptanoic acid (AP7, 30 or 60 mg/kg) was injected intraperitoneally between the first and second stimulation. Intensity of movements accompanying stimulation was diminished regularly only by CGP 40116. Duration of afterdischarges was reduced and intensity of clonic seizures was decreased by CGP 40116 in all age groups; dizocilpine exhibited similar action in 25- and 18-day-old rats, AP7 only in 25-day-old animals. Anticonvulsant action of the three NMDA antagonists exhibited different developmental profiles in our model; this difference might be due to developmental changes of NMDA receptors.
Insights
NMDA receptor antagonists show varying anticonvulsant effects in developing rats. CGP 40116 was effective across all ages, while dizocilpine and AP7 showed age-dependent activity, suggesting receptor development influences drug efficacy.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Epilepsy is a neurological disorder characterized by recurrent seizures.
- NMDA receptors play a crucial role in neuronal excitation and synaptic plasticity.
- Developing brains exhibit unique physiological characteristics that can influence drug responses.
Purpose of the Study:
- To evaluate the anticonvulsant properties of three NMDA receptor antagonists in developing rats.
- To investigate the developmental profile of NMDA receptor antagonist efficacy.
- To explore the potential role of developmental changes in NMDA receptors in drug response.
Main Methods:
- Epileptic afterdischarges were induced via sensorimotor cortex stimulation in rats aged 12, 18, and 25 days.
- Three NMDA receptor antagonists—dizocilpine, CGP 40116, and 2-amino-7-phosphonoheptanoic acid (AP7)—were administered intraperitoneally.
- The intensity of motor responses and the duration/intensity of afterdischarges and seizures were measured.
Main Results:
- CGP 40116 consistently reduced seizure duration and intensity across all age groups.
- Dizocilpine demonstrated anticonvulsant effects in 18- and 25-day-old rats, but not in 12-day-old rats.
- AP7 showed anticonvulsant activity only in the oldest group (25-day-old rats).
Conclusions:
- The anticonvulsant efficacy of NMDA receptor antagonists varies significantly with age in developing rats.
- Developmental changes in NMDA receptor function likely contribute to the observed age-dependent drug responses.
- These findings highlight the importance of considering neurodevelopmental stages when assessing potential antiepileptic drugs targeting NMDA receptors.
