We investigate the effects of thiorphan, a specific inhibitor of enkephalinase A and bestatin, a specific inhibitor of aminopeptidase, on the stereotyped behaviors induced by phencyclidine (PCP) in cannulated rats. The PCP-induced turning was significantly potentiated when thiorphan (50 μg) and bestatin (50 μg) were injected simultaneously into the rat lateral ventricle. The increase of PCP-induced turning was completely antagonized by the pretreatment with naloxone. Thiorphan (50 μg) or bestatin (50 μg) alone failed to potentiate PCP-induced turning. Thiorphan and/or bestatin did not affect significantly the PCP-induced head weaving and back-pedalling except that thiorphan (50 μg) potentiated the PCP-induced head weaving 15-18 min after the PCP injection. The combination of thiorphan and bestatin alone did not induce any behavioral change. These results suggest that thiorphan and bestatin produce an increase of endogenous enkephalins and that as a result, PCP-induced turning may be enhanced.
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