NEUROTENSIN, N-ACETYL-ASPARTYL-GLUTAMATE AND BETA-ENDORPHIN MODULATE [H-3] DOPAMINE RELEASE FROM GUINEA-PIG NUCLEUS-ACCUMBENS, PREFRONTAL CORTEX AND CAUDATE-PUTAMEN

Dopaminergic hyperactivity in nucleus accumbens and dopaminergic hypoa ctivity in prefrontal cortex are thought to underlie positive and nega tive symptoms of schizophrenia, respectively. The caudate putamen is t he neuroanatomical substrate for extrapyramidal side effects resulting from chronic antipsychotic treatment. We sought to identify potential endogenous regulators of dopamine release that might produce differen tial effects in these brain areas. We tested neurotensin, N-acetyl-asp artyl-glutamate and beta-endorphin for potential regulation of [H-3]do pamine release in these regions of guinea pig brain. All three peptide s stimulated dopamine release, above basal activity, at all concentrat ions tested in the three regions. Neurotensin significantly enhanced a nd N-acetyl-aspartyl-glutamate had no significant effect on N-methyl-D -aspartate-stimulated release from all three regions. In contrast, bet a-endorphin significantly inhibited N-methyl-D-aspartate-stimulated re lease in nucleus accumbens and caudate putamen, These results suggest that these neuropeptides may regulate endogenous dopamine release and therefore may be potential therapeutic targets for antipsychotic drug development.