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Molecular Pharmacology, Vol 12, 463-475, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Dopaminergic Neurons: Effects of Electrical Stimulation on Dopamine Biosynthesis

L. CHARLES MURRIN 1 and ROBERT H. ROTH 1

1 Departments of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06520

Electrical stimulation of the medial forebrain bundle was employed in order to study the effects of increased impulse flow on dopamine synthesis. Stimulation at frequencies ranging from 5 to 30 Hz resulted in an increase in the specific activity of dopamine isolated from the neostriatum 20 min after intravenous administration of [3H]tyrosine. The optimal frequency for this effect was 15 Hz. Similar results were found in the olfactory tubercles. Phenylalanine was also found to be a precursor for neostriatal dopamine. The increase in neostriatal dopamine specific activity following labeled precursor administration continued for 15 min after stimulation. About 99% of the total fraction of labeled catecholamines found in the neostriatum 20 min following tyrosine administration was identified as dopamine by Amberlite CG-120 column chromatography. Dopa accumulation following dopa decarboxylase inhibition was also increased by electrical stimulation. This increased accumulation of dopa continued for at least 15 min after stimulation. These data are discussed in terms of the ability of increased impulse flow to increase dopamine synthesis by altering the activity of tyrosine hydroxylase in dopaminergic neurons.

Note:
ACKNOWLEDGMENTS We would like to thank Dr. B. S. Bunney for his discussion of anatomical details, Dr. W. Scott of Hoffmann-La Roche for a generous supply of Ro 4-4602, Ms. Jan Abele and Ms. Karen Brady for their excellent technical assistance, and Ms. Lynn Bon-Tempo for her editorial and secretarial assistance.

Submitted on October 6, 1975




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