D-amphetamine (A)-induced dopamine (DA) release is not strictly dependent on newly-synthesized transmitter

Journal Article · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:7119423

Parker, E; Cubeddu, L

A is thought to exert its stimulant effects by releasing DA from a newly synthesized transmitter pool. This hypothesis was evaluated directly by measuring the basal efflux and electrically-evoked release of endogenous DA and dihydroxyphenylacetic acid (DOPAC). In striatal slices from reserpine-treated rabbits A increased DA efflux, reduced DOPAC efflux, and inhibited electrically-evoked /sup 3/H-ACh release in a concentration-dependent manner. These effects could not be mimicked by inhibition of neuronal uptake or MAO, but were blocked by inhibition of DA synthesis or neuronal uptake, and were potentiated by inhibition of MAO. In slices with intact vesicular transmitter stores A induced DA efflux was 2-fold greater than that seen in slices having no vesicular stores. Inhibition of DA synthesis reduced A-induced DA efflux by 60%, but had little effect on the ability of A to inhibit /sup 3/H-ACh release. A also increased the electrical stimulation-evoked overflow of DA (an effect which was attenuated slightly by synthesis inhibition), and potently inhibited DOPAC overflow. These results suggest that: 1) A facilitates efflux of axoplasmic DA by an accelerated exchange diffusion mechanism. The releasable axoplasmic pool is derived from newly synthesized and vesicular transmitter pools; 2) postsynaptic indices of transmitter release may be misleading; and 3) A increases electrically-evoked DA release possibly by inhibiting neuronal uptake.

• Research Organization: Univ. of North Carolina, Chapel Hill
• OSTI ID: 7119423
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AMPHETAMINES
ANALEPTICS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL EFFECTS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
DOPAMINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
RABBITS
SECRETION
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES