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Regulation of dopamine synthesis and release in striatal and prefrontal cortical brain slices

Thesis/Dissertation ·
OSTI ID:6478944
Brain slices were used to investigate the role of nerve terminal autoreceptors in modulating dopamine (DA) synthesis and release in striatum and prefrontal cortex. Accumulation of dihydroxyphenylalanine (DOPA) was used as an index of tyrosine hydroxylation in vitro. Nomifensine, a DA uptake blocker, inhibited DOPA synthesis in striatal but not prefrontal slices. This effect was reversed by the DA antagonist sulpiride, suggesting it involved activation of DA receptors by elevated synaptic levels of DA. The autoreceptor-selective agonist EMD-23-448 also inhibited striatal but not prefrontal DOPA synthesis. DOPA synthesis was stimulated in both brain regions by elevated K/sup +/, however only striatal synthesis could be further enhanced by sulpiride. DA release was measured by following the efflux of radioactivity from brain slices prelabeled with (/sup 3/H)-DA. EMD-23-448 and apomorphine inhibited, while sulpiride enhanced, the K/sup +/-evoked overflow of radioactivity from both striatal and prefrontal cortical slices. These findings suggest that striatal DA nerve terminals possess autoreceptors which modulate tyrosine hydroxylation as well as autoreceptors which modulate release. Alternatively, one site may be coupled to both functions through distinct transduction mechanisms. In contrast, autoreceptors on prefrontal cortical terminals appear to regulate DA release but not DA synthesis.
Research Organization:
Yale Univ., New Haven, CT (USA)
OSTI ID:
6478944
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
BIOSYNTHESIS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CHEMISTRY
DOPAMINE
DRUGS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MEMBRANE PROTEINS
NERVES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
POTASSIUM COMPOUNDS
PROTEINS
REACTION KINETICS
RECEPTORS
RESPONSE MODIFYING FACTORS
SYMPATHOMIMETICS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS