Cytosolic Ca2+ modulation of newly synthesized Ser-contained GABA-peptidesrelated to the antipsychotic action

The abnormal behaviours induced by phencyclidine (PCP : 10mg/kg) were measu red using behavioral analysis following either microinjection of newly synt hesized GABA-peptides, which block the high K-evoked cytosolic Ca2+ levels and dopamine release in a dose-dependent manner, into the rat caudate putam en or intraperitoneal injection. The i.p. administration of PCP induced the : hyperactivity and the stereotypy in a time-dependent manner, and the maxi mum activity was measured 30-45 min after the administration of PCP. This h yperactivity was sustained for more than two hours. Following microinjectio n of dose of 500 nmol of GABA, L-serine, D-serine and GABA-peptides (L-piva loyl-L-serine-leucyl-GABA, L-pivaloyl-D-serine-leucyl-GABA, N-pivaloyl-leuc yl-GABA) into the caudate putamen, each substance showed a different patter n of inhibition on PCP induced-hyperactivity and stereotypy. In particular, GABA-peptides reduced the hyperactivity more potent. Moreover, intraperito neal injection of these GABA-peptides showed reductive effect on the PCP-in duced abnormal behaviors. Particularly D-serine contained GABA-peptide show ed the most potent inhibition on the PCP-induced abnormal behaviors in all of the examined ligands. These results suggest that these novel Ca2+ modula tors, GABA-peptides, have the strong pharmacological properties as the anti schizophrenia drug.