LACK OF NEUROPROTECTIVE EFFECT OF SIGMA-RECEPTOR LIGANDS IN THE NEUROTOXICITY OF P-CHLOROAMPHETAMINE IN RAT-BRAIN

We studied the mechanism of antagonism of p-chloroamphetamine-induced neurotoxicity by dextromethorphan. The pretreatment with potent and se lective sigma receptor ligands, 4-phenyl-4-(1-phenylbutyl)piperidine ( 4-PPBP) and -2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohyd rochloride (NE-100), did not alter the reduction of 5-hydroxytryptamin e and 5-hydroxyindoleacetic acid in the cerebral cortex by repeated ad ministration of p-chloroamphetamine. These results suggest that sigma receptors might not play a significant role in the antagonism of p-chl oroamphetamine-induced neurotoxicity by dextromethorphan.