Regulation of dopamine synthesis in the medial prefrontal cortex: Studies in brain slices

Marina Wolf, M. P. Galloway, R. H. Roth

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The rapid firing rates and small dopamine (DA) pools that characterize mesoprefrontal DA neurons make these cells more vulnerable to release-dependent changes in intraneuronal DA levels than nigrostriatal DA neurons. In vivo studies of mesoprefrontal DA synthesis are therefore complicated by the necessity to distinguish between effects of dopaminergic drugs on synthesis-modulating autoreceptors and effects resulting from increased end product inhibition of tyrosine hydroxylase (TH) secondary to decreased DA release. We have used brain slices, in which impulse flow-dependent release is apparently attenuated, to compare regulation of tyrosine hydroxylation in striatal and prefrontal nerve terminals. Accumulation of DOPA after decarboxylase inhibition was used as an index of TH activity. Nomifensine, a DA uptake blocker, inhibited DOPA synthesis in striatal but not prefrontal slices. This effect was reversed stereoselectively by sulpiride, suggesting it involved activation of DA receptors by elevated synaptic levels of DA. DOPA synthesis was stimulated in both brain regions by elevated K+; however, only striatal synthesis could be further enhanced by sulpiride. This enhancement was dose dependent, stereoselective and significantly attenuated by EMD 23 448, a putative autoreceptor-selective DA agonist that does not exert direct inhibitory effects on TH activity in vitro. EMD 23 448 had no effect on prefrontal slices at concentrations that produce greater than 50% inhibition of striatal DOPA synthesis. These findings suggest: 1) released DA modulates TH activity in striatal slices via a receptor-mediated mechanism, independent of end product inhibitory effects, and 2) prefrontal DA terminals do not possess autoreceptors that modulate TH directly, consistent with studies in vivo indicating that DA agonists inhibit prefrontal synthesis by decreasing DA release and thereby increasing intraneuronal DA levels.

Original languageEnglish (US)
Pages (from-to)699-707
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume236
Issue number3
StatePublished - Jan 1 1986
Externally publishedYes

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Prefrontal Cortex
Dopamine
Corpus Striatum
Tyrosine 3-Monooxygenase
Brain
Autoreceptors
Sulpiride
Dopaminergic Neurons
Dopamine Agonists
Nomifensine
Dopamine Agents
Carboxy-Lyases
Dopamine Antagonists
Dopamine Receptors
Hydroxylation
Tyrosine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Regulation of dopamine synthesis in the medial prefrontal cortex : Studies in brain slices. / Wolf, Marina; Galloway, M. P.; Roth, R. H.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 236, No. 3, 01.01.1986, p. 699-707.

Research output: Contribution to journalArticle

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