The effects of chronic maternal perinatal nimodipine treatment on the immunocytochemical distribution of the Ca(2+)-binding proteins parvalbumin (PV) and S-100 beta in neocortex and hippocampus were studied at the age of postnatal day (PD) 5, 7, 10, 14 and 20. The Ca2+ antagonist nimodipine (1000 ppm BAY e 9736 in daily food) was administered to pregnant rats starting at postconceptual day 11. The expression of PV exemplified in layer V of parietal and retrosplenial cortex and in all hippocampal layers of CA1 and CA3 was enhanced by more than two-fold in the offspring of nimodipine-treated dams at PD 10 compared with placebo-treated animals. The difference was no longer present at PD 14 and 20. Nimodipine administration also significantly increased the number of S-100 beta-immunopositive glial cells in upper neocortical layers I-III at PD 5 and 7. Again, the difference between nimodipine and placebo-treated animals disappeared after PD 10. The data indicate an accelerated development of PV and S-100 immunoreactivity in the postnatal forebrain as a result of perinatal blockade of the L-type Ca2+ current.

The possibility of an involvement of peptidergic systems in schizophrenia has been under investigation for a number of years. Studies of the efficacy of des-tyr-gamma-endorphin were equivocal; more recent studies with des-enkephalin-gamma-endorphin have reported some activity but the peptide has only been investigated as an adjunct to neuroleptic medication, apart from one very small active reference comparator study. In the multicentre study reported here, 96 patients suffering from schizophrenia (DSM-III with a current exacerbation if chronic) were allocated randomly to double-blind treatment with either des-enkephalin-gamma-endorphin (DE-gamma-E) (Org 5878) 10 mg given as a once daily intramuscular injection for 4 weeks, thioridazine 400 mg orally in 2 divided doses or placebo using a double-dummy technique to preserve blindness. There was a significant advantage for thioridazine compared with placebo registered on all measures at weeks 3 and 4. There was no difference between DE-gamma-E and placebo. There was a significant difference between thioridazine and DE-gamma-E at weeks 3 and 4 registered on the MSS and at week 3 registered on the BPRS. The lack of efficacy of DE-gamma-E suggests that the theories that the endorphins have an important role in schizophrenia have to be revised. The need for well designed placebo controlled studies for assessing efficacy in schizophrenia is emphasized.