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Chronic Haloperidol Treatment Increases the Level of in Vitro Translatable Messenger Ribonucleic Acid Coding for the β-Endorphin/drenocorticotropin Precursor Proopiomelanocortin in the Pars Intermedia of the Rat Pituitary

Department of Neuropharmacology, Max-Planck-Institut für Psychiatrie D-8000 Munchen 40, Federal Republic of Germany

Address requests for reprints to: Dr. Volker Höllt, Department of Neuropharmacology, Max-Planck-Institut für Psychiatrie, Kraepelinstrasse 2, D-8000 Munchen 40, Federal Republic of Germany

Abstract

Chronic treatment of rats with haloperidol (1.5 mg/kg, once daily) over a period of 7–21 days resulted in a 80– 100% increase in the tissue levels of immunoreactive β-endorphin and in the in vitro release of immunoreactiveβ-endorphin from the neurointermediate pituitary. Incorporation of [³H]phenylalanine into isolated neurointermediate pituitaries of haloperidoltreated rats revealed an increase in the amount of label incorporated into the β-endorphin/ACTH precursor proopiomelanocortin (POMC) to a similar extent (about 80%) but had essentially no effect on the conversion of the precursor into β-lipotropin and β-endorphin. Extraction of messenger (m) RNA from neurointermediate pituitaries followed by cell-free translation in a reticulocyte system showed an increase in the total level of translatable mRNA (about 25%). The content of translatable mRNA coding for POMC, however, was increased by 100–150%. Time-course studies revealed a parallelism between the effect of haloperidol on the level of in vitro translatable mRNA coding for POMC and the ability of the drug to increase the concentrations ofβ-endorphin in the neurointermediate pituitary. A complete reversal of the effects of haloperidol was seen 2 weeks after discontinuation of the drug.

These findings suggest that the chronic blockade of dopaminergic receptors by haloperidol causes a reversible increase in theβ-endorphin biosynthesis in the rat intermediate pituitary at the pretranslational level by markedly increasing the level of translatable mRNA coding for POMC.

Received November 3, 1981.

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