RT Journal Article SR Electronic T1 Mesocortical Dopamine Neurons JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 270 OP 275 VO 19 IS 2 A1 MICHAEL J. BANNON A1 RICHARD L. MICHAUD A1 ROBERT H. ROTH YR 1981 UL http://molpharm.aspetjournals.org/content/19/2/270.abstract AB The regulation of dopamine (DA) synthesis in rat mesocortical DA neurons was studied and compared with DA synthesis in nigrostriatal DA neurons. The increase in striatal DA content caused by γ-butyrolactone (GBL) was reversed by activation of nerve-terminal DA autoreceptors by apomorphine. In contrast, the GBL-induced increase in prefrontal cortical DA was unaffected by DA agonists. By using the accumulation of dopa after the administration of the dopa decarboxylase inhibitor Ro4-4602 as an index of DA synthesis, it was demonstrated that the increase in striatal DA following GBL was due to an acceleration of DA synthesis. In contrast, GBL did not increase cortical dopa accumulation. However, GBL completely prevented the rapid decline of DA seen following α-methyltyrosine treatment, indicating that DA turnover had been inhibited in the mesocortical neurons, as has been previously demonstrated with other DA neurons. The monoamine oxidase inhibitor pargyline increased both striatal and cortical DA levels, leading to greatly attenuated dopa accumulation (tyrosine hydroxylation in vivo) in both regions. Finally, the DA antagonist haloperidol greatly accelerated striatal dopa accumulation, but effected only a modest change in cortical dopa accumulation, which was completely prevented by the GBL-induced inhibition of impulse flow. These results suggest that transmitter synthesis in the prefrontal cortical terminals of mesocortical DA neurons is subject to end product inhibition and is regulated by changes in neuronal impulse flow. However, the synthesis of DA in these terminals does not seem to be modulated by DA autoreceptors. ACKNOWLEDGMENTS The authors gratefully acknowledge the assistance of Anne Morrison both in the development of the sample preparation procedure and in the routine processing of brain tissue samples. We thank Sarah Wheeler for her advice on the cortical dissection technique. We also thank Lynn Williams for her assistance in the preparation of the manuscript. The Ro4-4602 used in these experiments was generously supplied by Dr. Scott of Hoffmann-LaRoche.