The
beta-carboline, methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (
DMCM), is a potent chemoconvulsant. While it has been utilized in adult rodents, it has not been previously examined for effects across postnatal development.
DMCM is a negative allosteric modulator of
benzodiazepine-sensitive GABAA receptors, receptor subtypes that are particularly enriched in limbic brain regions. This raises the possibility that
DMCM may be particularly effective at evoking forebrain
seizures, which is a challenge in neonatal animals due to the relative immaturity of the forebrain seizure network. The ability to selectebrain
seizures is desirable when screening for drugs to use in
temporal lobe epilepsy, which is characterized by
seizures within the forebrain (limbic) network. To determine the profile of
DMCM action across development, we examined the dose-dependent ability of
DMCM to induce
seizures in rats at P7, P10, P13, P14, P21 and in adulthood. We found that the highest sensitivity to
DMCM occurred in P10, P13, and P14 rats. The lowest sensitivity occurred in P21 rats. Neonatal (P7) and adult (P60+) rats displayed moderate sensitivity. With moderate (0.2-0.4 mg/kg) doses of
DMCM, we were able to reliably evoke limbic
motor seizures without tonic-clonic components in animals as young as P7. These data support the utility of
DMCM in assessing seizure threshold during development and raise the possibility for future exploration of
DMCM as an agent to screen
anticonvulsant drugs during the postnatal period.