Neurotensin, N-acetyl-aspartylglutamate and beta-endorphin modulate [3H]dopamine release from guinea pig nucleus accumbens, prefrontal cortex and caudate-putamen.

Dopaminergic hyperactivity in nucleus accumbens and dopaminergic hypoactivity in prefrontal cortex are thought to underlie positive and negative symptoms of schizophrenia, respectively. The caudate putamen is the neuroanatomical substrate for extrapyramidal side effects resulting from chronic antipsychotic treatment. We sought to identify potential endogenous regulators of dopamine release that might produce differential effects in these brain areas. We tested neurotensin, N-acetyl-aspartyl-glutamate and beta-endorphin for potential regulation of [3H]dopamine release in these regions of guinea pig brain. All three peptides stimulated dopamine release, above basal activity, at all concentrations tested in the three regions. Neurotensin significantly enhanced and N-acetyl-aspartyl-glutamate had no significant effect on N-methyl-D-aspartate-stimulated release from all three regions. In contrast, beta-endorphin significantly inhibited N-methyl-D-aspartate-stimulated release 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.