Incorporation of 4.5-3-H-leucine into the limbic system of ICR mice as a long-term effect of haloperidol application.

Following previous histological studies on the problem of so-called psychopharmacotoxic encephalopathy, we have mesured the incorporation of 3-H-4.5 leucine into the limbic systm (Ncl. amygdaloideus lateralis, Gyrus dentatus) of ICR mice following haloperidol treatments (0.16 and 1.6 mg/kg/d) lasting 4 weeks and 4 months respectively. The results were compared with those obtained by treatment for 10 days. Protein-incorporated activity was significantly elevated throughout treatment, but there were no significant differences between the treated and control animals 4 weeks after treatment had ended. Although the mechanism causing the differences during treatment is unknown, the results show clearly that, although some tolerance is developed, even long-term haloperidol treatment is accompanied by alteration of the protein and or amino acid metabolism which can contribute to neuronal decompensation.