Dextromethorphan does not protect against quinolinic acid neurotoxicity in rat striatum.

Dextromethorphan (DM, 40 or 80 mg/kg, i.p.) and MK-801 (3 or 10 mg/kg, i.p.) were compared in their ability to prevent the depletion of choline acetyltransferase (ChAT) activity in the rat striatum following intrastriatal injection of quinolinic acid. DM did not reduce striatal ChAT depletion following injection of either 300 or 150 nmol of quinolinic acid. Following injection of 300 nmol of quinolinic acid, MK-801 significantly reduced striatal ChAT depletion at a dose of 3 mg/kg and completely prevented striatal ChAT depletion at a dose of 10 mg/kg. In contrast to the potent neuroprotective action of MK-801, DM does not protect striatal cholinergic neurons from an acute challenge by an NMDA receptor agonist.