The effect of the combination of lithium and haloperidol on brain intermediary metabolism in vivo.

The effect of the chronic administration of the combination of lithium and haloperidol has been studied in rat brain in vivo. Lithium was administered in food in amounts sufficient to maintain serum lithium levels of 1.0 +/- 0.1 mEq/l; haloperidol (1.5 mg/kg) was given i.p. once daily. Control animals pair-fed with the lithium/haloperidol alone, or neither drug. Fifteen days after the beginning of the experiments the brains were instantaneously frozen with a rapid brain-freezing device and multiple metabolites were measured in the perchloric acid extract of the tissue. Intermediates examined included selected metabolites of the glycolytic pathway and the tricarboxylic acid cycle, N-acetylaspartate and cofactors such as ATP, CoA, and acetyl-CoA. Estimates of the effects of the treatments on cytoplasmic and mitochondrial redox states were also made. The results showed only minor effects of any of the treatments on any of the parameters studied and little or nothing to distinguish the combination of lithium and haloperidol from either treatment alone.