CONCURRENT LOCOMOTOR STIMULATION AND DECREASE IN DOPAMINE RELEASE IN RATS AND MICE AFTER TREATMENT WITH THE COMPETITIVE NMDA RECEPTOR ANTAGONISTS D-CPPENE AND CGS-19755

The present study was aimed al investigating the effects of the compet itive N-methyl-D-aspartate (NMDA) receptor antagonists D-CPPene 3-(2-c arboxypiperazine-4-yl)-propenyl-1-phosphonic acid) and CGS 19755 (cis- 4-(phosphonomethyl)piperidine-2-carboxylic acid) on dopamine (DA) tran smission and motor activity in mice and rats. As measures of DA releas e we used mouse brain 3-methoxytyramine (3-MT) levels, an indirect est imate of DA release, and striatal dialysate measures of DA in consciou s and freely moving rats by means of microdialysis. To obtain addition al information about monoaminergic neurotransmission, brain tissue lev els of DA, DOPAC, HVA, 5-HT and 5-HIAA were measured in both mice and rats. The animals were sacrificed at the time when NMDA antagonist-ind uced locomotor stimulation was maximal. In mice, D-CPPene and CGS 1975 5 decreased striatal 3-MT levels, whereas, in general, 3-MT levels in the limbic forebrain were not significantly altered. Treatment with CG S 19755 decreased rat striatal dialysate levels of DA but increased S- HIAA at time points when locomotor activity was increased. D-CPPene an d CGS 19755 have been observed to produce psychotic symptoms in man. T he present study suggests that these symptoms are not a result of an i ncrease in central dopamine release.