The mitochondrial inhibitor malonate enhances NMDA toxicity in the neonatal rat striatum.

Intra-striatal injections of the mitochondrial inhibitor malonate elicit age-dependent neuronal damage in rat brain; injury is more extensive in older animals than in young adults. We investigated the neurotoxic potential of malonate in the immature rat brain. We found that 7-day-old (P7) rats were highly resistant to malonate neurotoxicity. Yet, although intra-striatal injections of 1 mumol malonate did not elicit overt tissue injury in P7 rats, co-administration of this dose of malonate with a dose of NMDA close to its toxicity threshold (2.5 nmol) doubled the severity of resulting excitotoxic injury.