PAOPA, a potent analogue of Pro-Leu-glycinamide and allosteric modulator of the dopamine D2 receptor, prevents NMDA receptor antagonist (MK-801)-induced deficits in social interaction in the rat: Implications for the treatment of negative symptoms in schizophrenia

The aim of this study was to investigate whether a potent analogue of the endogenous brain peptide l-prolyl-l-leucyl-glycinamide (PLG), (3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA), can prevent the induction of social withdrawal caused by sub-chronic treatment with the non-competitive NMDA (N-methyl-l-aspartate) receptor antagonist, MK-801. Results indicate that MK-801 (0.5 mg/kg) significantly decreased social interaction following sub-chronic treatment (7 days). Treatment with PAOPA (1 mg/kg) blocked the effects of MK-801, and increased the amount of time spent in social interaction in comparison to control animals. These results provide evidence for the development of peptidomimetic compounds for the treatment of social withdrawal and related negative symptoms associated with schizophrenia.